Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow.

This type of cancer usually gets worse quickly if it is not treated. It is the most common type of acute leukemia in adults. AML is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, and acute non-lymphocytic leukemia. (National Cancer Institute [NCI], 2011) Normally, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. A lymphoid stem cell becomes a white blood cell. A myeloid stem cell becomes one of three types of mature blood cells:

Red blood cells that carry oxygen and other substances to all tissues of the body. White blood cells that fight infection and disease. Platelets that form blood clots to stop bleeding.

Acute Myeloid Leukemia Subtypes

AML is first described by its morphology (what the cancerous cells look like under the microscope). AML is classified by the type of normal, immature white blood cell it most closely resembles.

Most patients with AML have a subtype called myeloblastic leukemia, which means the cancer is in the cells that normally produce neutrophils. Other patients have a type of AML called monoblastic or monocytic leukemia. In monocytic leukemia, the cells look like white blood cells called monocytes. Leukemia cells can also be a mixture of myeloblastic and monocytic cells. Sometimes AML seems to come from cells that produce red blood cells (called erythroid) or platelets (called megakaryocytic). Acute promyelocytic leukemia (APL) is a unique subtype of AML where the cancer cell stops maturing when the cell is at a stage called the promyelocyte or progranulocyte stage. Flow cytometry is a blood test that can identify particular proteins on the surface of abnormal cells and is sometimes used to find the difference among these subtypes.

Acute Lymphocytic Leukemia (ALL), also known as Acute Lymphoblastic Leukemia - This is the most common type of leukemia among young children, although adults can get it as well, especially those over the age of 65. Survival rates of at least five years range from 85% among children and 50% among adults. The following are all subtypes of this leukemia: precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, Burkitt's leukemia, and acute biphenotypic leukemia. Chronic Lymphocytic Leukemia (CLL) - This is most common among adults over 55, although younger adults can get it as well. CLL hardly ever affects children. The majority of patients with CLL are men, over 60%. 75% of treated CLL patients survive for over five years. Experts say CLL is incurable. A more aggressive form of CLL is B-cell prolymphocytic leukemia. Acute Myelogenous Leukemia (AML) - AML is more common among adults than children, and affects males significantly more often than females. Patients are treated with chemotherapy. 40% of treated patients survive for over 5 years. The following are subtypes of AMS - acute promyelocytic leukemia, acute myeloblastic leukemia, and acute megakaryoblastic leukemia. Chronic Myelogenous Leukemia (CML) - The vast majority of patients are adults. 90% of treated patients survive for over 5 years. Gleevec (imatinib) is commonly used to treat CML, as well as some other drugs. Chronic monocytic leukemia is a subtype of CML.

Etiology
Several factors have been implicated in the causation of AML, including antecedent hematologic disorders, familial syndromes, environmental exposures, and drug exposures. However, most patients who present with de novo AML have no identifiable risk factor.

Antecedent hematologic disorders

The most common risk factor for AML is the presence of an antecedent hematologic disorder, the most common of which is myelodysplastic syndrome(MDS). MDS is a bone marrow disease of unknown etiology that occurs most often in older patients and manifests as progressive cytopenias that occur over months to years. Patients with low-risk MDS (eg, refractory anemia with normal cytogenetics findings) generally do not develop AML, whereas patients with high-risk MDS (eg, refractory anemia with excess blasts-type 2) frequently do.

Other antecedent hematologic disorders that predispose patients to AML includeaplastic anemia, myelofibrosis, paroxysmal nocturnal hemoglobinuria, andpolycythemia vera.

Congenital disorders
Some congenital disorders that predispose patients to AML include Bloom syndrome, Down syndrome, congenital neutropenia, Fanconi anemia, andneurofibromatosis. Usually, these patients develop AML during childhood; rarely, some may present in young adulthood. More subtle genetic disorders, including polymorphisms of enzymes that metabolize carcinogens, also predispose patients to AML. For example, polymorphisms of NAD(P)H:quinone oxidoreductase (NQO1), an enzyme that metabolizes benzene derivatives, are associated with an increased risk of AML.[3]Particularly increased risk exists for AML that occurs after chemotherapy for another disease or for de novo AML with an abnormality of chromosomes 5, 7, or both. Likewise, polymorphisms in glutathione S -transferase are associated with secondary AML after chemotherapy for other malignancies.[4]

Familial syndromes
Germline mutations in the gene AML1 (RUNX1, CBFA2) occur in the familial platelet disorder with predisposition for AML, an autosomal dominant disorder characterized by moderate thrombocytopenia, a defect in platelet function, and propensity to develop AML.[5] Mutation of CEBPA (the gene encoding CCAAT/enhancer binding protein alpha, a granulocytic differentiation factor and member of the bZIP family) was described in a family with 3 members affected by AML. [6] Taskesen et al evaluated concurrent gene mutations, clinical outcome, and gene expression signatures of CEBPA double versus single mutations in 1182 patients with cytogenetically-normal AML (CN-AML) (aged 16-60 y).[7] Both double-mutatedCEBPA and single-mutated CEBPA were associated with favorable outcome compared with wild type CEBPA (5-year overall survival (OS), 63% and 56% versus 39%; P < .0001 and P=.05, respectively). However, in multivariable analysis, only double=mutated CEBPA was a prognostic factor for favorable outcome. Some hereditary cancer syndromes, such as Li-Fraumeni syndrome, can manifest as leukemia. However, cases of leukemia are less common than the solid tumors that generally characterize these syndromes.

Environmental exposures
Several studies demonstrate a relationship between radiation exposure and leukemia. Early radiologists (before the use of appropriate shielding) were found to have an increased likelihood of developing leukemia. Patients receiving therapeutic irradiation for ankylosing spondylitis were at increased risk of leukemia. Survivors of the atomic bomb explosions in Japan were at a markedly increased risk for the development of leukemia. Persons who smoke have a small but statistically significant (odds ratio, 1.5) increased risk of developing AML.[8] In several studies, the risk of AML was slightly increased in people who smoked compared with those who did not smoke. Exposure to benzene is associated with aplastic anemia and pancytopenia. These patients often develop AML. Many of these patients demonstrate M6 morphology.

Previous exposure to chemotherapeutic agents

As more patients with cancer survive their primary malignancy and more patients receive intensive chemotherapy (including bone marrow transplantation [BMT]), the number of patients with AML increases because of exposure to chemotherapeutic agents. For example, the cumulative incidence of acute leukemia in patients with breast cancer who were treated with doxorubicin and cyclophosphamide as adjuvant therapy was 0.2-1.0% at 5 years.[9]

Patients with previous exposure to chemotherapeutic agents can be divided into 2 groups: (1) those with previous exposure to alkylating agents and (2) those with exposure to topoisomerase-II inhibitors. Patients with a previous exposure to alkylating agents, with or without radiation, often have a myelodysplastic phase before the development of AML. Cytogenetics testing frequently reveals -5 and/or -7 (5q- or monosomy 7). Patients with a previous exposure to topoisomerase-II inhibitors do not have a myelodysplastic phase. Cytogenetics testing reveals a translocation that involves band 11q23. Less commonly, patients developed leukemia with other balanced translocations, such as inversion 16 or t(15;17). [10] The typical latency period between drug exposure and acute leukemia is approximately 3-5 years for alkylating agents/radiation exposure, but it is only 9-12 months for topoisomerase inhibitors.

Classification of AML
In the FAB (French-American-British) system AML is divided into 8 types, MO to M7. The classification is based on the type of cell and its degree of maturity. The pathologist examines the malignant cells under light microscopy. There are other types of classification systems, such as the WHO (World Health Organization) one. Below are the eight FAB subtypes:

M0 - minimally differentiated acute myeloblastic leukemia. This type is rarely seen M1 - acute myeloblastic leukemia, without maturation. 15% of all cases are of this type. M2 - acute myeloblastic leukemia, with granulocytic maturation. 25% of all cases are of this type M3 - promyelocytic, or acute promyelocytic leukemia (APL). 10% of all cases are of this type M4 - acute myelomonocytic leukemia. 25% of all cases are of this type M4eo - myelomonocytic together with bone marrow eosinophilia. This type is rarely seen M5 - acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b). 10% of all cases are of this type M6 - acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b). This type is rarely seen M7 - acute megakaryoblastic leukemia. This type is rarely seen M8 - acute basophilic leukemia. This type is rarely seen

Risk factors
By Mayo Clinic staff Living With Cancer
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Sign up now Factors that may increase your risk of acute myelogenous leukemia include: Increasing age. The risk of acute myelogenous leukemia increases with age. Acute myelogenous leukemia is most common in adults age 65 and older.

Your sex. Men are more likely to develop acute myelogenous leukemia than are women. Previous cancer treatment. People who've had certain types of chemotherapy and radiation therapy or treatment for childhood acute lymphocytic leukemia (ALL) may have a greater risk of developing AML.

Exposure to radiation. People exposed to very high levels of radiation, such as survivors of a nuclear reactor accident, have an increased risk of developing AML.

Dangerous chemical exposure. Exposure to certain chemicals, such as benzene which is found in unleaded gasoline and used by the chemical industry also is linked to greater risk of AML.

Smoking. AML is linked to cigarette smoke, which contains benzene and other known cancer-causing chemicals.

Other blood disorders. People who've had another blood disorder, such as myelodysplasia, polycythemia vera or thrombocythemia, are at greater risk of developing AML.

Genetic disorders. Certain genetic disorders, such as Down syndrome, are associated with an increased risk of AML. Many people with AML have no known risk factors, and many people who have risk factors never develop the cancer.