Acute myeloid leukemia
Classification & external resources

Bone marrow aspirate showing acute myeloid leukemia. Arrows indicate Auer rods.
ICD-10	C92.0
ICD-9	205.0
ICD-O:	M9861/3
OMIM	602439
DiseasesDB	203
eMedicine	med/34

Acute myeloid leukemia (AML), also known as acute myelogenous leukemia, is a cancer of the myeloid line of white blood cells, characterized by the rapid proliferation of abnormal cells which accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age. Although AML is a relatively rare disease, accounting for approximately 1.2% of cancer deaths in the United States,^[1] its incidence is expected to increase as the population ages. Image File history File links Download high-resolution version (1548x1440, 3965 KB) Summary Bone marrow aspirate showing acute myeloid leukemia. ... Bone marrow aspirate showing acute myeloid leukemia with Auer rods in several blasts Auer rods can be seen in the leukemic blasts of Acute Myeloid Leukemia. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // C00-D48 - Neoplasms (C00-C14) Malignant neoplasms, lip, oral cavity and pharynx (C00) Malignant neoplasm of lip (C01) Malignant neoplasm of base of tongue (C02) Malignant neoplasm of other and unspecified parts of tongue (C03) Malignant neoplasm of gum (C04) Malignant neoplasm of floor of mouth (C05) Malignant neoplasm of... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... Myeloid cells is a subsummating term for all hemopoietic cells except the lymphoid ones (T-cells, B-cells, NK-cells, dendritic cells). ... “White Blood Cells” redirects here. ... This article does not cite any references or sources. ... Diagram that shows the development of different blood cells from hematopoietic stem cell to mature cells Haematopoiesis (from Ancient Greek: haima blood; poiesis to make) (or hematopoiesis in the United States; sometimes also haemopoiesis or hemopoiesis) is the formation of blood cellular components. ...

The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, resulting in a drop in red blood cells, platelets, and normal white blood cells. These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. Although several risk factors for AML have been identified, the specific cause of AML remains unclear. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated. “Red cell” redirects here. ... A 250 ml bag of newly collected platelets. ...

Acute myeloid leukemia is a potentially curable disease; but only a minority of patients are cured with current therapy. AML is treated initially with chemotherapy aimed at inducing a remission; some patients may go on to receive a hematopoietic stem cell transplant. Chemotherapy is the use of chemical substances to treat disease. ... Remission is the state of absence of disease activity in patients with known chronic illness. ... Bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ...

Areas of active research in acute myeloid leukemia include further elucidation of the cause of AML, identification of better prognostic indicators, development of new methods of detecting residual disease after treatment, and the development of new drugs and targeted therapies. Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctors prediction of how a patients disease will progress, and whether there is chance of recovery. ... Targeted cancer therapy is a type of chemotherapy which blocks the growth of cancer cells by interfering specific targeted molecules needed for carcinogenesis and tumor growth. ...

History

The first published description of a case of leukemia in medical literature dates to 1827, when a French physician named Alfred-Armand-Louis-Marie Velpeau described a 63-year-old florist who developed an illness characterized by fever, weakness, urinary stones, and substantial enlargement of the liver and spleen. Velpeau noted that the blood of this patient had a consistency "like gruel", and speculated that the appearance of the blood was due to white corpuscles.^[2] In 1845, a series of patients who died with enlarged spleens and changes in the "colors and consistencies of their blood" was reported by the Edinburgh-based pathologist J.H. Bennett; he used the term "leucocythemia" to describe this pathological condition.^[3] Year 1827 (MDCCCXXVII) was a common year starting on Monday (link will display the full calendar) of the Gregorian Calendar (or a common year starting on Wednesday of the 12-day slower Julian calendar). ... Alfred-Armand-Louis-Marie Velpeau (May 18, 1795 - August 24, 1867) was a French anatomist and surgeon who was born in a village near Tours. ... Kidney stones are solid accretions (crystals) of dissolved minerals in urine found inside the kidneys or ureters. ... Hepatosplenomegaly is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). ... 1845 was a common year starting on Wednesday (see link for calendar). ... For other uses, see Edinburgh (disambiguation). ... To meet Wikipedias quality standards, this article or section may require cleanup. ...

The term "leukemia" was coined by Rudolf Virchow, the renowned German pathologist, in 1856. As a pioneer in the use of the light microscope in pathology, Virchow was the first to describe the abnormal excess of white blood cells in patients with the clinical syndrome described by Velpeau and Bennett. As Virchow was uncertain of the cause of the white blood cell excess, he used the purely descriptive term "leukemia" (Greek: "white blood") to refer to the condition.^[4] [[ Rudolf Ludwig Karl Virchow (born October 13, 1821, in Schivelbein (Pomerania); died September 5, 1902, in Berlin) was a German doctor, anthropologist, public health activist, pathologist, prehistorian, biologist and politician. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... 1856 was a leap year starting on Tuesday (see link for calendar). ... 1852 microscope Compound microscope made by John Cuff in 1750 A microscope (Greek: micron = small and scopos = aim) is an instrument for viewing objects that are too small to be seen by the naked or unaided eye. ...

Further advances in the understanding of acute myeloid leukemia occurred rapidly with the development of new technology. In 1877, Paul Ehrlich developed a technique of staining blood films which allowed him to describe in detail normal and abnormal white blood cells. Wilhelm Ebstein introduced the term "acute leukemia" in 1889 to differentiate rapidly progressive and fatal leukemias from the more indolent chronic leukemias.^[5] The term "myeloid" was coined by Neumann in 1869, as he was the first to recognize that white blood cells were made in the bone marrow (Greek: µυєλός, myelos = (bone) marrow) as opposed to the spleen. The technique of bone marrow examination to diagnose leukemia was first described in 1879 by Mosler.^[6] Finally, in 1900 the myeloblast, which is the malignant cell in AML, was characterized by Naegeli, who divided the leukemias into myeloid and lymphocytic.^{[7] [8]} 1877 (MDCCCLXXVII) was a common year starting on Monday (see link for calendar). ... Paul Ehrlich Paul Ehrlich in his workroom Paul Ehrlich (March 14, 1854 – August 20, 1915) was a German scientist who won the 1908 Nobel Prize in Physiology or Medicine. ... Staining is a biochemical technique of adding a class-specific (DNA, proteins, lipids, carbohydrates) dye to a substrate to qualify or quantify the presence of a specific compound. ... Wilhelm Ebstein (November 27, 1836, Jauer, Prussian Silesia - October 22, 1912) was a German physician. ... Year 1889 (MDCCCLXXXIX) was a common year starting on Tuesday (link will display the full calendar) of the Gregorian calendar (or a common year starting on Sunday of the 12-day slower Julian calendar). ... Chronic leukemia may refer to: Chronic myelogenous leukemia Chronic lymphocytic leukemia Hairy cell leukemia Category: ... The spleen is an organ located in the abdomen, where it functions in the destruction of old red blood cells and holding a reservoir of blood. ... A bone marrow biopsy is a medical procedure used as part of a test in the diagnosis of several conditions including leukemia. ... 1879 (MDCCCLXXIX) was a common year starting on Wednesday (see link for calendar). ... Äž: For the film, see: 1900 (film). ... Myeloblasts or blasts are new, immature blood cells developed in the bone marrow that are the precursors of myelocytes. ...

Signs and symptoms

Most signs and symptoms of AML are due to an increased number of malignant white blood cells displacing or otherwise interfering with production of normal blood cells in the bone marrow. A lack of normal white blood cell production makes the patient susceptible to infections (while the leukemic cells themselves are derived from white blood cell precursors, they have no infection-fighting capacity).^[9] A lack of red blood cells (anemia) can cause fatigue, paleness, and shortness of breath. A lack of platelets can lead to easy bruising or bleeding with minor trauma. Diagram that shows the development of different blood cells from hematopoietic stem cell to mature cells Haematopoiesis (from Ancient Greek: haima blood; poiesis to make) (or hematopoiesis in the United States; sometimes also haemopoiesis or hemopoiesis) is the formation of blood cellular components. ... This article does not cite any references or sources. ... This article discusses the medical condition. ... A 250 ml bag of newly collected platelets. ...

The early signs of AML are often non-specific, and may be similar to those of influenza or other common illnesses. Some generalized symptoms include fever, fatigue, weight loss or loss of appetite, shortness of breath with exertion, anemia, easy bruising or bleeding, petechiae (flat, pin-head sized spots under the skin caused by bleeding), bone pain and joint pain and persistent or frequent infections.^[9] Influenza, commonly known as flu, is an infectious disease of birds and mammals caused by an RNA virus of the family Orthomyxoviridae (the influenza viruses). ... This article needs additional references or sources for verification. ... The word fatigue is used in everyday living to describe a range of afflictions, varying from a general state of lethargy to a specific work induced burning sensation within muscle. ... Weight loss, in the context of medicine or health or physical fitness, is a reduction of the total body weight, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue. ... Anorexia (deriving from the Greek όρεξη (orexe) = appetite) is the decreased sensation of appetite. ... Dyspnea (R06. ... This article discusses the medical condition. ... A bruise or contusion or ecchymoses is a kind of injury, usually caused by blunt impact, in which the capillaries are damaged, allowing blood to seep into the surrounding tissue. ... For other uses, see Bleeding (disambiguation). ... minor Petechia A petechia (IPA pronunciation: ), plural petechiae (IPA pronunciation: ) is a small red or purple spot on the body, caused by a minor hemorrhage (broken capillary blood vessels). ... Bone Pain- Bone pain is generally referred to as having pain within the affected bone. ... In medicine, arthralgia (literally: joint pain, from arthros = joint and -algia denoting pain) is the presence of painful joints in the absence of frank arthritis. ... Infection is also the title of an episode of the television series Babylon 5; see Infection (Babylon 5). ...

Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in AML, in contrast to acute lymphoblastic leukemia. The skin is involved about 10% of the time in the form of leukemia cutis. Rarely, Sweet's syndrome, a paraneoplastic inflammation of the skin, can occur with AML.^[9] Splenomegaly is an enlargement of the spleen, which usually lies in the left upper quadrant (LUQ) of the human abdomen. ... In medicine, a disease is asymptomatic when it is at a stage where the patient does not experience symptoms. ... Lymphadenopathy is a term meaning disease of the lymph nodes. ... Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a form of leukemia, characterised by the overproduction and continuous multiplication of malignant and immature white blood cells (also known as lymphoblasts) in the bone marrow. ... A chloroma is a solid tumor composed of immature white blood cells called myeloid precursor cells. ... Sweets syndrome, or acute febrile neutrophilic dermatosis, is a condition characterized by the sudden onset of fever, leukocytosis, and tender, erythematous, well-demarcated papules and plaques which show dense neutrophilic infiltrates on histologic examination. ... A paraneoplastic phenomenon is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. ...

Some patients with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue. Rarely, the first sign of leukemia may be the development of a solid leukemic mass or tumor outside of the bone marrow, called a chloroma. Occasionally, a person may show no symptoms, and the leukemia may be discovered incidentally during a routine blood test.^[10] This article does not cite any references or sources. ... A chloroma is a solid tumor composed of immature white blood cells called myeloid precursor cells. ... In medicine, a disease is asymptomatic when it is at a stage where the patient does not experience symptoms. ...

Causes

A number of risk factors for developing AML have been identified, including:

• "Pre-leukemic" blood disorders such as myelodysplastic or myeloproliferative syndromes can evolve into AML; the exact risk depends on the type of MDS/MPS.^[11]
• Exposure to anti-cancer chemotherapy, in particular alkylating agents, can increase the risk for the subsequent development of AML. The risk is highest about 3–5 years after chemotherapy.^[12] Other chemotherapy agents, specifically epipodophyllotoxins and anthracyclines, have also been associated with treatment-related leukemia. These treatment-related leukemias are often associated with specific chromosomal abnormalities in the leukemic cells.^[13]
• Ionizing radiation exposure can increase the risk of AML. Survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of AML,^[14] as did radiologists exposed to high levels of X-rays prior to the adoption of modern radiation safety practices.^[15]
• Occupational chemical exposure to benzene and other aromatic organic solvents is controversial as a cause of AML. Benzene and many of its derivatives are known to be carcinogenic in vitro. While some studies have suggested a link between occupational exposure to benzene and increased risk of AML,^[16] others have suggested that the attributable risk, if any, is slight.^[17]
• Several congenital conditions may increase the risk of leukemia; the most common is probably Down syndrome, which is associated with a 10- to 18-fold increase in the risk of AML.^[18]

The myelodysplastic syndromes (MDS, formerly known as preleukemia) are a diverse collection of hematological conditions united by ineffective production of blood cells and varying risks of transformation to acute myelogenous leukemia. ... The myeloproliferative diseases (MPDs) are a group of diseases of the bone marrow where excess cells are produced. ... Chemotherapy is the use of chemical substances to treat disease. ... An alkylating antineoplastic agent is an alkylating agent that attaches an alkyl group to DNA. Since cancer cells generally divide more rapidly than do healthy cells they are more sensitive to DNA damage, and alkylating agents are used clinically to treat a variety of tumours. ... Podophyllin is a drug obtained from the rhizome of the American Mayapple (‘’Podophyllum peltatum’’), an herbaceous perennial belonging to the natural order Berberidaceae, indigenous in woods in Canada and the United States. ... Anthracycline - Wikipedia, the free encyclopedia /**/ @import /skins-1. ... Radiation hazard symbol. ... The mushroom cloud over Hiroshima after the dropping of Little Boy. ... Radiology is the branch of medical science dealing with the medical use of x-ray machines or other such radiation devices. ... In the NATO phonetic alphabet, X-ray represents the letter X. An X-ray picture (radiograph) taken by Röntgen An X-ray is a form of electromagnetic radiation with a wavelength approximately in the range of 5 pm to 10 nanometers (corresponding to frequencies in the range 30 PHz... For benzine, see petroleum ether. ... A solvent is a liquid that dissolves a solid, liquid, or gaseous solute, resulting in a solution. ... In pathology, a carcinogen is any substance or agent that promotes cancer. ... A congenital disorder is a medical condition or defect that is present at or before birth (for example, congenital heart disease). ...

Epidemiology

Acute myeloid leukemia is a relatively rare cancer. There are approximately 10,500 new cases each year in the United States, and the incidence rate has remained stable from 1995 through 2005. AML accounts for 1.2% of all cancer deaths in the United States.^[1] The incidence of disease is defined as the number of new cases of disease occurring in a population during a defined time interval. ...

The incidence of AML increases with age; the median age at diagnosis is 63 years. AML accounts for about 90% of all acute leukemias in adults, but is rare in children.^[1] The rate of therapy-related AML (that is, AML caused by previous chemotherapy) is rising; therapy-related disease currently accounts for about 10–20% of all cases of AML.^[19] AML is slightly more common in men, with a male-to-female ratio of 1.3:1.^[20]

There is some geographic variation in the incidence of AML. In adults, the highest rates are seen in North America, Europe, and Oceania, while adult AML is rarer in Asia and Latin America.^[21][22] In contrast, childhood AML is less common in North America and India than in other parts of Asia.^[23] These differences may be due to population genetics, environmental factors, or a combination of the two. North America North America is a continent[1] in the Earths northern hemisphere and (chiefly) western hemisphere. ... For other uses, see Europe (disambiguation). ... For other uses, see Oceania (disambiguation). ... For other uses, see Asia (disambiguation). ... Latin America consists of the countries of South America and some of North America (including Central America and some the islands of the Caribbean) whose inhabitants mostly speak Romance languages, although Native American languages are also spoken. ...

A hereditary risk for AML appears to exist. There are numerous reports of multiple cases of AML developing in a family at a rate higher than predicted by chance alone.^{[24][25][26][27]} The risk of developing AML is increased threefold in first-degree relatives of patients with AML.^[28] The relationships and names of various family members in the English language. ...

Pathophysiology

The malignant cell in AML is the myeloblast. In normal hematopoiesis, the myeloblast is an immature precursor of myeloid white blood cells; a normal myeloblast will gradually mature into a mature white blood cell. However, in AML, a single myeloblast accumulates genetic changes which "freeze" the cell in its immature state and prevent differentiation.^[29] Such a mutation alone does not cause leukemia; however, when such a "differentiation arrest" is combined with other mutations which disrupt genes controlling proliferation, the result is the uncontrolled growth of an immature clone of cells, leading to the clinical entity of AML.^[30] Myeloblasts or blasts are new, immature blood cells developed in the bone marrow that are the precursors of myelocytes. ... Diagram that shows the development of different blood cells from hematopoietic stem cell to mature cells Haematopoiesis (from Ancient Greek: haima blood; poiesis to make) (or hematopoiesis in the United States; sometimes also haemopoiesis or hemopoiesis) is the formation of blood cellular components. ... Myeloid cells is a subsummating term for all hemopoietic cells except the lymphoid ones (T-cells, B-cells, NK-cells, dendritic cells). ... Embryonic stem cells differentiate into cells in various body organs. ... The Knudson hypothesis is the hypothesis that cancer is the result of accumulated mutations to a cells DNA. It was first proposed by Carl O. Nordling in 1953, [1][2] and later formulated by Alfred G. Knudson in 1971. ... The term cell growth is used in two different ways in biology. ...

Much of the diversity and heterogeneity of AML stems from the fact that leukemic transformation can occur at a number of different steps along the differentiation pathway.^[31] Modern classification schemes for AML recognize that the characteristics and behavior of the leukemic cell (and the leukemia) may depend on the stage at which differentiation was halted.

Specific cytogenetic abnormalities can be found in many patients with AML; the types of chromosomal abnormalities often have prognostic significance.^[32] The chromosomal translocations encode abnormal fusion proteins, usually transcription factors whose altered properties may cause the "differentiation arrest."^[33] For example, in acute promyelocytic leukemia, the t(15;17) translocation produces a PML-RARα fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid-specific genes and inhibits myeloid differentiation.^[34] A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ... Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctors prediction of how a patients disease will progress, and whether there is chance of recovery. ... Chromosomal translocation of the 4th and 20th chromosome. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... In the context of genetics, a transcription factor is a regulatory protein that initiates the transcription of certain genes upon binding with DNA. The binding of a transcription factor to a specific DNA sequence can result in either an increased rate of transcription of the gene, known as activated transcription... Acute myelogenous leukemia (AML), also known as acute myeloid leukemia, is a cancer of the myeloid line of white blood cells. ... A fusion protein is a protein created through genetic engineering from two or more proteins/peptides. ... Retinoic acid, or Retin-A or vitamin A acid, is a carotenoid organic compound that is a component of visual pigments. ...

The clinical signs and symptoms of AML result from the fact that, as the leukemic clone of cells grows, it tends to displace or interfere with the development of normal blood cells in the bone marrow.^[35] This leads to neutropenia, anemia, and thrombocytopenia. The symptoms of AML are in turn often due to the low numbers of these normal blood elements. In rare cases, patients can develop a chloroma, or solid tumor of leukemic cells outside the bone marrow, which can cause various symptoms depending on its location.^[9] Neutropenia (or neutropaenia, adjective neutrop(a)enic) is a hematological disorder characterized by an abnormally low number of neutrophil granulocytes (a type of white blood cell). ... This article discusses the medical condition. ... Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... A chloroma is a solid tumor composed of immature white blood cells called myeloid precursor cells. ...

Diagnosis

The first clue to a diagnosis of AML is typically an abnormal result on a complete blood count. While an excess of abnormal white blood cells (leukocytosis) is a common finding, and leukemic blasts are sometimes seen, AML can also present with isolated decreases in platelets, red blood cells, or even with a low white blood cell count (leukopenia).^[36] While a presumptive diagnosis of AML can be made via examination of the peripheral blood smear when there are circulating leukemic blasts, a definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy Schematics of shorthand for complete blood count commonly used by physicians. ... Leukocytosis is an elevation of the white blood cell count (the leukocyte count) above the normal range. ... A 250 ml bag of newly collected platelets. ... “Red cell” redirects here. ... Leukopenia or leukocytopenia refers to a decrease in the number of circulating white blood cells (leukocytes) in the blood. ...

A bone marrow examination is often performed to identify the type of abnormal blood cells; however, if there are many leukemic cells circulating in the peripheral blood, a bone marrow biopsy may not be necessary. Marrow or blood is examined via light microscopy as well as flow cytometry to diagnose the presence of leukemia, to differentiate AML from other types of leukemia (e.g. acute lymphoblastic leukemia), and to classify the subtype of disease (see below). A sample of marrow or blood is typically also tested for chromosomal translocations by routine cytogenetics or fluorescent in situ hybridization. A bone marrow biopsy is a medical procedure used as part of a test in the diagnosis of several conditions including leukemia. ... Brain biopsy A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... Microscopy is any technique for producing visible images of structures or details too small to otherwise be seen by the human eye. ... Analysis of a marine sample of photosynthetic picoplankton by flow cytometry showing three different populations (Prochlorococcus, Synechococcus and picoeukaryotes) Flow cytometry is a technique for counting, examining and sorting microscopic particles suspended in a stream of fluid. ... Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a form of leukemia, characterised by the overproduction and continuous multiplication of malignant and immature white blood cells (also known as lymphoblasts) in the bone marrow. ... Chromosomal translocation of the 4th and 20th chromosome. ... A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ... A metaphase cell positive for the bcr/abl rearrangement using FISH. The chromosomes can be seen in blue. ...

The diagnosis and classification of AML can be challenging, and should be performed by a qualified hematopathologist or hematologist. In straightforward cases, the presence of certain morphologic features (such as Auer rods) or specific flow cytometry results can distinguish AML from other leukemias; however, in the absence of such features, diagnosis may be more difficult.^[37] Hematopathology is the branch of pathology which studies diseases of hematopoietic cells (see below). ... A physician specialising in the treatment of blood diseases. ... Bone marrow aspirate showing acute myeloid leukemia with Auer rods in several blasts Auer rods can be seen in the leukemic blasts of Acute Myeloid Leukemia. ...

According to the widely used WHO criteria, the diagnosis of AML is established by demonstrating involvement of more than 20% of the blood and/or bone marrow by leukemic myeloblasts.^[38] AML must be carefully differentiated from "pre-leukemic" conditions such as myelodysplastic or myeloproliferative syndromes, which are treated differently. Look up who in Wiktionary, the free dictionary. ... Myeloblasts or blasts are new, immature blood cells developed in the bone marrow that are the precursors of myelocytes. ... The myelodysplastic syndromes (MDS, formerly known as preleukemia) are a diverse collection of hematological conditions united by ineffective production of blood cells and varying risks of transformation to acute myelogenous leukemia. ... The myeloproliferative diseases (MPDs) are a group of diseases of the bone marrow where excess cells are produced. ...

Because acute promyelocytic leukemia (APL) has the highest curability and requires a unique form of treatment, it is important to quickly establish or exclude the diagnosis of this subtype of leukemia. Fluorescent in situ hybridization performed on blood or bone marrow is often used for this purpose, as it readily identifies the chromosomal translocation (t[15;17]) that characterizes APL.^[39] Acute myelogenous leukemia (AML), also known as acute myeloid leukemia, is a cancer of the myeloid line of white blood cells. ... A metaphase cell positive for the bcr/abl rearrangement using FISH. The chromosomes can be seen in blue. ... Chromosomal translocation of the 4th and 20th chromosome. ...

Classification

The two most commonly used classification schemata for AML, as of 2006, are the older French-American-British (FAB) system and the newer World Health Organization (WHO) system. 2006 is a common year starting on Sunday of the Gregorian calendar. ... “WHO” redirects here. ...

French-American-British classification

The French-American-British (FAB) classification system divided AML into 8 subtypes, M0 through to M7, based on the type of cell from which the leukemia developed and its degree of maturity. This is done by examining the appearance of the malignant cells under light microscopy and/or by using cytogenetics to characterize any underlying chromosomal abnormalities. The subtypes have varying prognoses and responses to therapy. Although the WHO classification (see below) may be more useful, the FAB system is still widely used as of mid-2006. There are at least three French-American-British (FAB) classification systems; they are used to describe different sets of hematologic diseases: FAB classification of acute lymphoblastic leukemias FAB classification of acute myeloid leukemias FAB classification of myelodysplastic syndromes Categories: | ... Microscopy is any technique for producing visible images of structures or details too small to otherwise be seen by the human eye. ... A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ...

The eight FAB subtypes are:^[40]

• M0 (undifferentiated AML)
• M1 (myeloblastic, without maturation)
• M2 (myeloblastic, with maturation)
• M3 (promyelocytic), or acute promyelocytic leukemia (APL)
• M4 (myelomonocytic)
• M4eo (myelomonocytic together with bone marrow eosinophilia)
• M5 monoblastic leukemia (M5a) or monocytic leukemia (M5b)
• M6 (erythrocytic), or erythroleukemia
• M7 (megakaryoblastic)

Pluripotential hemopoietic stem cells or pluripotential hematopoietic stem cells (PHSCs) are stem cells found in the bone marrow. ... It has been suggested that this article or section be merged into acute myeloid leukemia. ... Acute myelogenous leukemia (AML), also known as acute myeloid leukemia, is a cancer of the myeloid line of white blood cells. ... Eosinophils are white blood cells that are responsible for combating infection by parasites in the body. ... Monocytic leukemia is a type of myeloid leukemia characterized by a dominance of monocytes in the marrow. ... Monocytic leukemia is a type of leukemia characterized by a dominance of monocytes in the marrow. ... Erythroleukemia (or acute Di Guglielmo syndrome) is a rare form of acute myeloid leukemia where the myeloproliferation is of erythrocyte precursors. ...

World Health Organization classification

The World Health Organization (WHO) classification of acute myeloid leukemia attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria. Each of the WHO categories contains numerous descriptive sub-categories of interest to the hematopathologist and oncologist; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the five subtypes listed below. “WHO” redirects here. ... Hematopathology is the branch of pathology which studies diseases of hematopoietic cells (see below). ... Please refer to cancer for the biology of malignant disease, as well as a list of malignant diseases. ...

The WHO subtypes of AML are:^[41]

• AML with characteristic genetic abnormalities, which includes AML with translocations between chromosome 8 and 21 [t(8;21)], inversions in chromosome 16 [inv(16)], or translocations between chromosome 15 and 17 [t(15;17)]. Patients with AML in this category generally have a high rate of remission and a better prognosis compared to other types of AML.
• AML with multilineage dysplasia. This category includes patients who have had a prior myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD) that transforms into AML. This category of AML occurs most often in elderly patients and often has a worse prognosis.
• AML and MDS, therapy-related. This category includes patients who have had prior chemotherapy and/or radiation and subsequently develop AML or MDS. These leukemias may be characterized by specific chromosomal abnormalities, and often carry a worse prognosis.
• AML not otherwise categorized. Includes subtypes of AML that do not fall into the above categories.
• Acute leukemias of ambiguous lineage. Acute leukemias of ambiguous lineage (also known as mixed phenotype or biphenotypic acute leukemia) occur when the leukemic cells can not be classified as either myeloid or lymphoid cells, or where both types of cells are present.

The myeloproliferative diseases (MPDs) are a group of diseases of the bone marrow in which excess cells are produced. ...

Prognosis

Chromosomal translocation (9;11), associated with AML

Acute myeloid leukemia is a curable disease; the chance of cure for a specific patient depends on a number of prognostic factors.^[42] chromosome translocation 9;11 File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ... chromosome translocation 9;11 File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ...

Cytogenetics and prognosis in AML

The single most important prognostic factor in AML is cytogenetics, or the chromosomal structure of the leukemic cell. Certain cytogenetic abnormalities are associated with very good outcomes (for example, the (15;17) translocation in acute promyelocytic leukemia). About half of AML patients have "normal" cytogenetics; they fall into an intermediate risk group. A number of other cytogenetic abnormalities are known to associate with a poor prognosis and a high risk of relapse after treatment.^[43][44][45] A metaphase cell positive for the bcr/abl rearrangement using FISH Cytogenetics is the study of the structure of chromosome material. ... Acute myelogenous leukemia (AML), also known as acute myeloid leukemia, is a cancer of the myeloid line of white blood cells. ...

The first publication to address cytogenetics and prognosis was the MRC trial of 1998:^[46]

Later, the Southwest Oncology Group and Eastern Cooperative Oncology Group,^[47] and later still, Cancer and Leukemia Group B published other, mostly overlapping lists of cytogenetics prognostication in leukemia^[48] The Southwest Oncology Group (SWOG) is a National Cancer Institute (NCI) sponsored organization that conducts clinical trials in adult cancers. ... The Eastern Cooperative Oncology Group (ECOG) was established in 1955 as one of the first cooperative groups launched to perform multi-center cancer clinical trials. ... CALGB logo Cancer and Leukemia Group B (CALGB) is a cancer research cooperative group in the United States. ...

Antecedent MDS and prognosis

AML which arises from a pre-existing myelodysplastic syndrome or myeloproliferative disease (so-called secondary AML) has a worse prognosis, as does treatment-related AML arising after chemotherapy for another previous malignancy. Both of these entities are associated with a high rate of unfavorable cytogenetic abnormalities.^[49][50][51] The myeloproliferative diseases (MPDs) are a group of diseases of the bone marrow in which excess cells are produced. ... Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctors prediction of how a patients disease will progress, and whether there is chance of recovery. ...

Other prognostic markers

In some studies, age >60 years and elevated lactate dehydrogenase level were also associated with poorer outcomes.^[52] As with most forms of cancer, performance status (i.e. the general physical condition and activity level of the patient) plays a major role in prognosis as well. Lactate dehydrogenase (LDH) is an enzyme (EC 1. ...

FLT3 internal tandem duplications (ITDs) have been shown to confer a poorer prognosis in AML.^[53] Treating these patients with more aggressive therapy, such as stem-cell transplantation in first remission, has not been shown to enhance long-term survival, so this prognostic feature is of uncertain clinical significance at this point.^[54] CD135 is a cytokine receptor expressed on the surface of hematopoietic progenitor cells. ...

Researchers are investigating the clinical significance of c-KIT mutations^[55] in AML. These are prevalent, and clinically relevant because of the availability of tyrosine kinase inhibitors, such as sunitinib and imatinib that can block the activity of c-KIT pharmacologically. A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein. ... A kinase inhibitor is a type of enzyme inhibitor which specifically blocks the action of protein kinase. ... Sunitinib (marketed as Sutent, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. ... Imatinib is a drug used to treat certain types of cancer. ... A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein. ...

Other genes being investigated as prognostic factors or therapeutic targets include CEBPA, BAALC, ERG, and NPM1.

Overall expectation of cure

Cure rates in clinical trials have ranged from 20–45%;^[56][57] however, it should be noted that clinical trials often include only younger patients and those able to tolerate aggressive therapies. The overall cure rate for all patients with AML (including the elderly and those unable to tolerate aggressive therapy) is likely lower. Cure rates for promyelocytic leukemia can be as high as 98%.^[58]

Treatment

Treatment of AML consists primarily of chemotherapy, and is divided into two phases: induction and postremission (or consolidation) therapy. The goal of induction therapy is to achieve a complete remission by reducing the amount of leukemic cells to an undetectable level; the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure. Chemotherapy is the use of chemical substances to treat disease. ...

Induction

As of 2006, all FAB subtypes except M3 are usually given induction chemotherapy with cytarabine (ara-C) and an anthracycline (such as daunorubicin or idarubicin).^[59] Other alternatives, including high-dose ara-C alone, may also be used.^[60][61] Because of the toxic effects of therapy, including myelosuppression and an increased risk of infection, induction chemotherapy may not offered to the very elderly. Induction chemotherapy usually requires a hospitalization of about 1 month to receive the chemotherapy and recover from its side effects. 2006 is a common year starting on Sunday of the Gregorian calendar. ... Cytarabine is a shortened form of cytosine arabinoside, a commonly used chemotherapy agent used mainly in the treatment of leukemia and non-Hodgkin lymphoma. ... Anthracycline - Wikipedia, the free encyclopedia /**/ @import /skins-1. ... Daunorubicin or daunomycin (daunomycin cerubidine) is chemotherapy of the anthracycline family that is given as a treatment for some types of cancer. ... Idarubicin chemical structure Idarubicin or 4-demethoxydaunorubicin is an anthracycline drug that is used in the treatment of cancer. ... Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. ...

Induction chemotherapy is known as "7 and 3" because the cytarabine is given as a continuous IV infusion for seven consecutive days, while the anthracycline is given for three consecutive days as an IV push. Up to 70% of patients will achieve a remission with this protocol.^[62] Cytarabine is a shortened form of cytosine arabinoside, a commonly used chemotherapy agent used mainly in the treatment of leukemia and non-Hodgkin lymphoma. ... Anthracycline - Wikipedia, the free encyclopedia /**/ @import /skins-1. ...

The M3 subtype of AML, also known as acute promyelocytic leukemia, is almost universally treated with the drug ATRA (all-trans-retinoic acid) in addition to induction chemotherapy.^[63][64][65] Care must be taken to prevent disseminated intravascular coagulation (DIC), complicating the treatment of APL when the promyelocytes release the contents of their granules into the peripheral circulation. APL is eminently curable with well-documented treatment protocols. Acute myelogenous leukemia (AML), also known as acute myeloid leukemia, is a cancer of the myeloid line of white blood cells. ... Atra or ATRA can refer to: Stachybotrys chartarum All-trans retinoic acid This is a disambiguation page — a navigational aid which lists pages that might otherwise share the same title. ... Disseminated intravascular coagulation (DIC) is a pathological process in the body where the blood starts to coagulate throughout the whole body. ... Acute myelogenous leukemia (AML), also known as acute myeloid leukemia, is a cancer of the myeloid line of white blood cells. ... APL is an abbreviation, acronym, or initialism that may refer to: APL (programming language), an array programming language invented in 1962 Above Poverty Line, the section of people who can can fulfil their minimum basic needs Accreditation of Prior Learning, a continuing education method Acute promyelocytic leukemia, a subtype of...

The goal of the induction phase is to reach a complete remission. Complete remission does not mean that the disease has been cured; rather, it signifies that no disease can be detected with available diagnostic methods (i.e., <5% leukemic cells remain in the bone marrow).^[59] Complete remission is obtained in about 50%–75% of newly diagnosed adults, although this may vary based on the prognostic factors described above.^[66] This article does not cite any references or sources. ...

The durability of remission depends on the prognostic features of the original leukemia. In general, all remissions will fail without consolidation (post-remission) chemotherapy, and consolidation has become an important component of treatment.^[67]

Consolidation

Even after complete remission is achieved, leukemic cells likely remain in numbers too small to be detected with current diagnostic techniques. If no further postremission or consolidation therapy is given, almost all patients will eventually relapse.^[68] Therefore, more therapy is necessary to eliminate non-detectable disease and prevent relapse — that is, to achieve a cure.

The specific type of postremission therapy is individualized based on a patient's prognostic factors (see above) and general health. For good-prognosis leukemias (i.e. inv(16), t(8;21), and t(15;17)), patients will typically undergo an additional 3–5 courses of intensive chemotherapy, known as consolidation chemotherapy.^[69][70] For patients at high risk of relapse (e.g. those with high-risk cytogenetics, underlying MDS, or therapy-related AML), allogeneic stem cell transplantation is usually recommended if the patient is able to tolerate a transplant and has a suitable donor. The best postremission therapy for intermediate-risk AML (normal cytogenetics or cytogenetic changes not falling into good-risk or high-risk groups) is less clear and depends on the specific situation, including the age and overall health of the patient, the patient's personal values, and whether a suitable stem cell donor is available.^[70] Bone marrow transplantation or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ...

Relapsed AML

Despite aggressive therapy, however, only 20%–30% of patients enjoy long-term disease-free survival. For patients with relapsed AML, the only proven potentially curative therapy is a stem cell transplant, if one has not already been performed.^[71][72][73] In 2000, Mylotarg (gemtuzumab zogamicin) was approved in the United States for patients aged more than 60 years with relapsed AML who are not candidates for high-dose chemotherapy.^[74] Bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ... Gemtuzumab ozogamicin (marketed as Mylotarg) is a monoclonal antibody used to treat acute myelogenous leukemia. ...

Patients with relapsed AML who are not candidates for stem cell transplantion, or who have relapsed after a stem cell transplant, should be strongly considered for enrollment in a clinical trial, as conventional treatment options are limited. Agents under investigation include cytotoxic drugs such as clofarabine as well as targeted therapies such as farnesyl transferase inhibitors, decitabine, and inhibitors of MDR1 (multidrug-resistance protein). Since treatment options for relapsed AML are so limited, another option which may be offered is palliative care. In health care, including medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a process in which a medicine or other medical treatment is tested for its safety and effectiveness, often in comparison to existing treatments. ... Clofarabine: chemical structure Clofarabine is a substance that is being studied in the treatment of cancer. ... Targeted cancer therapy is a type of chemotherapy which blocks the growth of cancer cells by interfering specific targeted molecules needed for carcinogenesis and tumor growth. ... The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras protein, which is commonly abnormally active in cancer. ... Palliative care (from Latin palliare, to cloak) is any form of medical care or treatment that concentrates on reducing the severity of disease symptoms, rather than providing a cure. ...

For relapsed acute promyelocytic leukemia (APL), arsenic trioxide has been tested in trials and approved by the Food and Drug Administration. Like ATRA, arsenic trioxide does not work with other subtypes of AML.^[75] R-phrases , , , S-phrases , , , Supplementary data page Structure and properties n, εr, etc. ... “FDA” redirects here. ...

See also

• Chloroma
• Chronic myelogenous leukemia
• Acute lymphoblastic leukemia

A chloroma is a solid tumor composed of immature white blood cells called myeloid precursor cells. ... Chronic myelogenous leukemia (CML) is a form of chronic leukemia characterized by increased and unregulated clonal production of predominantly myeloid cells in the bone marrow. ... Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a form of leukemia, characterised by the overproduction and continuous multiplication of malignant and immature white blood cells (also known as lymphoblasts) in the bone marrow. ...

Further reading

• Martin Abeloff; James Armitage, John Niederhuber, Michael Kastan, W. Gillies McKenna (2004). Clinical Oncology, 3rd. edition, St. Louis, Mo.: Elsevier Churchill Livingstone. ISBN 0-443-06629-9. 
• Ronald Hoffman; Edward Benz, Jr., Sanford Shattil, Bruce Furie, Harvey Cohen, Leslie Silberstein, Philip McGlave (2005). Hematology: Basic Principles and Practice, 4th. edition, St. Louis, Mo.: Elsevier Churchill Livingstone. ISBN 0-443-06629-9. 

The Gateway Arch, shown here behind the Old Courthouse, is the most recognizable part of the St. ... Imprint of a medical publishing company owned by Elsevier Ltd, but previously owned by Harcourt and Pearsons. ... The Gateway Arch, shown here behind the Old Courthouse, is the most recognizable part of the St. ... Imprint of a medical publishing company owned by Elsevier Ltd, but previously owned by Harcourt and Pearsons. ...

References