Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising, bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.
Risk factors include getting older, being male, smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes for which treatments and outcomes may vary.
The first-line treatment of AML is usually chemotherapy, intending to induce remission. People may then go on to receive additional chemotherapy, radiation therapy, or a stem cell transplant. The specific genetic mutations present within the cancer cells may guide therapy, as well as determine how long that person is likely to survive.
Between 2017 and 2025, 12 new agents have been approved for AML in the U.S., including venetoclax (BCL2 inhibitor), gemtuzumab ozogamicin (CD33 antibody-drug conjugate), and several inhibitors targeting FMS-like tyrosine kinase 3, isocitrate dehydrogenase, and other pathways. Additionally, therapies like CPX351 and oral formulations of azacitidine and decitabine-cedazuridine have been introduced. Ongoing research is exploring menin inhibitors and other antibody-drug conjugates.
Low-intensity treatment with azacitidine plus venetoclax has emerged as the most effective option for older or unfit AML patients, based on a network meta-analysis of 26 trials involving 4,920 participants. It showed the highest survival and remission rates, with low-dose cytarabine (LDAC) plus glasdegib and LDAC plus venetoclax also showing clinical benefit.
In 2015, AML affected about one million people and resulted in 147,000 deaths globally. It most commonly occurs in older adults. Males are affected more often than females. , the five-year survival rate was about 35% in people under 60 years old and 10% in people over 60 years old. Older people whose health is too poor for intensive chemotherapy have a typical survival of five to ten months. It accounts for roughly 1.1% of all cancer cases, and 1.8% of cancer deaths in the United States.
Signs and symptoms
Most signs and symptoms of AML are caused by the crowding out in bone marrow of space for normal blood cells to develop. A lack of normal white blood cell production makes people more susceptible to infections. A low red blood cell count (anemia) can cause fatigue, paleness, shortness of breath and palpitations. A lack of platelets can lead to easy bruising, bleeding from the nose (epistaxis), small blood vessels on the skin (petechiae) or gums, or bleeding with minor trauma. Other symptoms may include fever, fatigue worse than what can be attributed to anemia alone, weight loss, and loss of appetite.
Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in most types of AML, except for acute myelomonocytic leukemia (AMML). The skin can be involved in the form of leukemia cutis; Sweet's syndrome; or non-specific findings: flat lesions (macules), raised lesion papules, pyoderma gangrenosum and vasculitis.
Some people with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue. Involvement of other parts of the body, such as the gastrointestinal tract, respiratory tract, and other parts, is possible but less common. One area which has particular importance for treatment is whether there is involvement of the meninges around the central nervous system. +Frequency of Symptoms on Initial Diagnosis of AMLSymptomFrequency (Adult)Frequency (Pediatric)Frequency (Overall)Fever76%85%48-80%Fatigue63%40%33-54%Bleeding28%32%20-29%Pallor84%85%~85%Lymphadenopathy30%55%12-40%Hepatomegaly23%38%22-29%Splenomegaly21%27%23-37%Enlarged gums15%11%~13%Bone or body pain - -~7%
Subtypes of AML The following are common AML subtypes:
AML with specific genetic abnormalities: An example is acute promyelocytic leukemia. Acute promyelocytic leukemia: A unique type of AML that is highly treatable.
AML with myelodysplasia-related changes: A disorder often seen in those with myelodysplasia-related blood cancers and in the elderly population as well. Therapy-related AML (t-AML): AML that has developed after chemotherapy or radiation therapy. AML with gene mutations: A category of subtypes that may qualify for targeted therapies. AML not otherwise specified (NOS)
Risk factors Most cases of AML do not have exposure to any identified risk factors. However, several risk factors for developing AML have been identified. These include other blood disorders, chemical exposures, ionizing radiation, and genetic risk factors. Where a defined exposure to past chemotherapy, radiotherapy, toxin or hematologic malignancy is known, this is termed secondary AML.
Other blood disorders Other blood disorders, particularly myelodysplastic syndrome (MDS) and less commonly myeloproliferative neoplasms (MPN), can evolve into AML; the exact risk depends on the type of MDS/MPN. The presence of asymptomatic clonal hematopoiesis also raises the risk of transformation into AML.
Chemical exposure Exposure to chemotherapy, in particular alkylating antineoplastic agents, can increase the risk of subsequently developing AML. Other chemotherapy agents, including fludarabine, and topoisomerase II inhibitors are also associated with the development of AML; most commonly after 4–6 years and 1–3 years respectively. These are often associated with specific chromosomal abnormalities in the leukemic cells.
Other chemical exposures associated with the development of AML include benzene, chloramphenicol, and phenylbutazone. The use of Agent Orange, a militarized herbicide used in the Vietnam War has been associated with the risk of AML due to the herbicide regularly having been contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin known.
Radiation High amounts of ionizing radiation exposure, such as that used for radiotherapy used to treat some forms of cancer, can increase the risk of AML. People treated with ionizing radiation after treatment for prostate cancer, non-Hodgkin lymphoma, lung cancer, and breast cancer have the highest chance of acquiring AML, but this increased risk returns to the background risk observed in the general population after 12 years. Historically, survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of AML, as did radiologists exposed to high levels of X-rays prior to the adoption of modern radiation safety practices.
Genetics Traditionally, AML was considered sporadic, with only a few exceptions associated with rare hereditary conditions such as Down syndrome, Fanconi anemia, and telomere biology disorders. With the introduction of Next Generation Sequencing (NGS) in clinical work-up, it is now estimated that up to 5–15% of all AML cases carry a pathogenic variant in a cancer susceptibility gene. Myeloid neoplasm with germline predisposition is recognized as a distinct category in the WHO 2022 classification of haematolymphoid tumors.
Other factors Being overweight and obese increase the risk of developing AML, as does any amount of active smoking. For reasons that may relate to substance or radiation exposure, certain occupations have a higher rate of AML; particularly work in the nuclear power industry, electronics or computer manufacturing, fishing, and animal slaughtering and processing.
Pathophysiology
The malignant cell in AML is the myeloblast. In normal development of blood cells (hematopoiesis), the myeloblast is an immature precursor of myeloid white blood cells; a normal myeloblast will mature into a white blood cell such as an eosinophil, basophil, neutrophil, or monocyte. In AML, though, a single myeloblast accumulates genetic changes that stop maturation, increase its proliferation, and protect it from programmed cell death (apoptosis). Much of the diversity and heterogeneity of AML is because leukemic transformation can occur at several different steps along the differentiation pathway. Genetic abnormalities or the stage at which differentiation was halted form part of modern classification systems.
Specific cytogenetic abnormalities can be found in many people with AML; the types of chromosomal abnormalities often have prognostic significance. The chromosomal translocations encode abnormal fusion proteins, usually transcription factors whose altered properties may cause the "differentiation arrest". For example, in APL, the t(15;17) translocation produces a PML-RARA fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid-specific genes and inhibits myeloid differentiation.
The clinical signs and symptoms of AML result from the growth of leukemic clone cells, which tend to interfere with the development of normal blood cells in the bone marrow. This leads to neutropenia, anemia, and thrombocytopenia. Other symptoms can arise from the infiltration of malignant cells into parts of the body, such as the gingiva and skin.
Many cells develop mutations in genes that affect epigenetics, such as DNA methylation. When these mutations occur, it is likely in the early stages of AML. Such mutations include in the DNA demethylase TET2 and the metabolic enzymes IDH1 and IDH2, which lead to the generation of a novel oncometabolite, D-2-hydroxyglutarate, which inhibits the activity of epigenetic enzymes such as TET2. Epigenetic mutations may lead to the silencing of tumor suppressor genes and/or the activation of proto-oncogenes.
Diagnosis
A complete blood count, which is a blood test, is one of the initial steps in the diagnosis of AML. It may reveal an excess of white blood cells (leukocytosis) or a decrease (leukopenia), and a low red blood cell count (anemia) and a low platelet count (thrombocytopenia) can also be commonly seen. A blood film may show leukemic blast cells. Inclusions within the cells called Auer rods, when seen, make the diagnosis highly likely. A definitive diagnosis requires a bone marrow aspiration and biopsy.
Bone marrow is examined under 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 provide information about how mature or immature the affected cells are, which can assist in classifying the subtype of disease. A sample of marrow or blood is typically also tested for chromosomal abnormalities by routine cytogenetics or fluorescent in situ hybridization. Genetic studies may also be performed to look for specific mutations in genes such as FLT3, nucleophosmin, and KIT, which may influence disease outcome.
Cytochemical stains on blood and bone marrow smears are helpful in the distinction of AML from ALL, and in the subclassification of AML. The combination of a myeloperoxidase or Sudan black stain and a nonspecific esterase stain will provide the desired information in most cases. The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL. The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiated monoblastic leukemia from ALL.