by Jason Wasserman MD PhD FRCPC and David Li MD
December 16, 2025
Acute myeloid leukemia is a type of blood cancer that starts in the bone marrow, the soft tissue inside bones that makes blood cells. In acute myeloid leukemia, immature blood cells called blasts grow too quickly and do not develop into normal, working blood cells. As blasts accumulate, they crowd out healthy cells, and the bone marrow cannot make enough normal red blood cells, white blood cells, and platelets. This can lead to anemia, infections, and bleeding.
Acute myeloid leukemia is called “acute” because it can worsen quickly over days to weeks if it is not treated. The leukemia cells can also move from the bone marrow into the blood and sometimes to other parts of the body.
What are the symptoms of acute myeloid leukemia?
The symptoms of acute myeloid leukemia develop because the bone marrow is no longer able to make enough normal blood cells. As leukemia blasts build up, they crowd out healthy cells, leading to low blood counts.
Low red blood cells, a condition called anemia, can cause fatigue, weakness, shortness of breath, dizziness, and pale skin. Many people describe feeling unusually tired or lacking energy, even with simple daily activities.
Low platelets can lead to easy bruising or bleeding. This may include frequent nosebleeds, bleeding gums, prolonged bleeding from minor cuts, or tiny red or purple spots on the skin caused by bleeding under the surface.
Low or poorly functioning white blood cells increase the risk of infection. People may develop frequent infections, infections that are hard to clear, or fevers without an apparent cause.
Some people experience bone or joint pain due to the crowding of leukemia cells inside the bone marrow. Swollen lymph nodes or enlargement of the liver or spleen can also occur, which may cause a feeling of fullness or discomfort in the abdomen.
Symptoms often develop quickly over days to weeks and may worsen rapidly if treatment is not started.
What causes acute myeloid leukemia?
Acute myeloid leukemia is caused by acquired genetic changes that occur in developing myeloid cells in the bone marrow. These changes affect genes that normally control how blood cells grow, mature, and stop dividing. As a result, immature myeloid cells (blasts) begin to grow uncontrollably and fail to develop into normal, functioning blood cells.
In many cases, these genetic changes involve specific chromosomal rearrangements, gene fusions, or mutations characteristic of acute myeloid leukemia. Examples include changes involving genes such as PML, RARA, RUNX1, CBFB, KMT2A, NPM1, FLT3, CEBPA, and others. Identifying these changes is important because they help define the subtype of acute myeloid leukemia and guide treatment decisions.
For most people, there is no apparent reason why these genetic changes occur. However, certain factors can increase the risk of developing acute myeloid leukemia. These include prior chemotherapy or radiation therapy for another cancer, exposure to high levels of radiation or certain chemicals, and pre-existing blood disorders such as myelodysplastic syndromes or myeloproliferative neoplasms.
Although rare inherited genetic conditions can increase the risk of acute myeloid leukemia, most cases are not inherited and are not passed on to children.
How is this diagnosis made?
The diagnosis of acute myeloid leukemia is made using blood tests, examination of blood and bone marrow under the microscope, and special laboratory tests that look at proteins and genetic changes in the leukemia cells. These steps apply to all types of acute myeloid leukemia, although the exact tests ordered may vary based on the situation.
Blood tests and peripheral blood findings
Most people have a complete blood count that shows low red blood cell, platelet, and white blood cell counts. Some people have a very high white blood cell count instead. Blasts are often seen in the blood, but the number can vary. A blood smear is examined to identify blasts and assess whether the cells exhibit features that suggest a specific subtype, such as Auer rods.
Bone marrow biopsy and aspirate
Bone marrow aspiration and biopsy are usually needed to confirm the diagnosis. The bone marrow is often hypercellular, meaning it contains too many cells for the patient’s age, because blasts occupy space. The pathologist counts the percentage of blasts and looks for signs of maturation, dysplasia, or patterns that suggest a particular subtype. In some situations, especially when there is scarring, the aspirate may be challenging to interpret, making the biopsy especially important.
Flow cytometry and immunophenotyping.
Flow cytometry tests which proteins are present on the surface or inside the leukemia cells. This helps confirm that the blasts are myeloid and helps separate acute myeloid leukemia from other blood cancers, such as acute lymphoblastic leukemia. Immunophenotyping is also important for identifying specific subtypes, including acute myeloid leukemia with minimal differentiation and megakaryoblastic forms.
Genetic and molecular tests
Genetic testing looks for chromosome changes and gene mutations that define the subtype, and help guide treatment and prognosis. Tests may include chromosome analysis, FISH, and molecular tests such as PCR or next-generation sequencing. Some changes, such as PML::RARA, RUNX1::RUNX1T1, CBFB::MYH11, NPM1, and CEBPA, are especially important because they strongly influence risk and treatment decisions. Some tests are also used after treatment to detect small amounts of residual leukemia, called minimal residual disease.
What are blasts, and why is the percentage of blasts important?
Blasts are very immature blood-forming cells. In healthy bone marrow, blasts are present in very small numbers and then mature into working red blood cells, white blood cells, or platelets.
In acute myeloid leukemia, blasts increase because they multiply but do not mature properly. In most cases, acute myeloid leukemia is diagnosed when blasts make up 20 percent or more of the cells in the bone marrow or blood. A higher blast percentage usually means the bone marrow has less room to make normal blood cells, which helps explain symptoms such as fatigue, infections, and bleeding. Blast percentage is also used to monitor response to treatment.
What does it mean if the bone marrow is described as hypercellular?
When bone marrow is described as hypercellular, it means there are too many blood-forming cells for the patient’s age. In acute myeloid leukemia, this often happens because blasts build up and crowd out healthy cells. This can lead to anemia, infections, and bleeding.
What does it mean if the bone marrow is described as normocellular?
Normocellular bone marrow has the expected balance of blood-forming cells and fat for a person’s age. In people being treated for acute myeloid leukemia, a normocellular marrow is a positive sign, indicating the bone marrow is recovering and beginning to produce healthy blood cells again.
What are the disease subtypes of acute myeloid leukemia?
Pathologists divide acute myeloid leukemia into subtypes based on the molecular or genetic changes in the leukemia cells. These changes can include fusions, in which two genes join together; mutations, which are changes in DNA; or rearrangements, in which a gene is moved or disrupted. Knowing the subtype matters because it helps doctors estimate prognosis and select treatment. When no defining genetic change is found, pathologists classify acute myeloid leukemia based on how the leukemia cells look and what proteins they express.
Subtypes with specific molecular changes
Acute promyelocytic leukemia with PML::RARA fusion
Acute promyelocytic leukemia is a subtype of acute myeloid leukemia caused by a fusion of two genes called PML and RARA. This fusion blocks normal development of white blood cells, leading to a build-up of abnormal cells called promyelocytes.
People may have typical acute myeloid leukemia symptoms such as fatigue, infections, bruising, and bleeding. A significant concern in this subtype is a dangerous bleeding and clotting problem called disseminated intravascular coagulation. This happens because platelet counts are often low, and the body’s clotting system becomes abnormal, which can cause severe bleeding if not treated quickly.
The diagnosis is confirmed by molecular testing for the PML::RARA fusion. Under the microscope, the abnormal cells may contain Auer rods, which are needle-shaped structures inside the cell.
With modern treatment, this subtype has an excellent prognosis. Many people are treated with all-trans retinoic acid and arsenic trioxide, sometimes with added chemotherapy in higher-risk cases. Long-term remission is common, and acute promyelocytic leukemia is considered one of the most curable types of leukemia.
Acute myeloid leukemia with RUNX1::RUNX1T1 fusion
This subtype is caused by a fusion between two genes called RUNX1 and RUNX1T1. The fusion disrupts normal blood cell development, leading to the accumulation of blasts.
Symptoms are usually related to low blood counts, including fatigue, infections, and bleeding. Some people develop myeloid sarcoma, a solid mass of leukemia cells outside the bone marrow.
Under the microscope, blasts may contain Auer rods. The leukemia cells often express proteins such as CD34 and myeloperoxidase and may also express CD19, which is more commonly associated with lymphoid cells. Additional mutations, especially in the KIT gene, can affect prognosis and response to treatment.
This subtype often responds well to intensive chemotherapy, commonly including high-dose cytarabine. Monitoring for minimal residual disease is important because it can detect small numbers of remaining leukemia cells and help predict relapse.
Acute myeloid leukemia with CBFB::MYH11 fusion
This subtype occurs when CBFB and MYH11 join together. This change interferes with proteins that normally regulate the maturation of myeloid cells.
People often present with fatigue, infections, bruising, or bleeding. White blood cell counts are usually high, and myeloid sarcoma can occur.
Microscopically, blood and bone marrow may show increased blasts and abnormal eosinophils with unusually large, dark granules. The leukemia cells often express markers such as CD34, KIT, and myeloperoxidase. The diagnosis is confirmed by identifying the CBFB::MYH11 fusion or related chromosomal changes, such as inv(16) or t(16;16). Additional mutations in genes such as RAS or KIT may influence the outcome.
This subtype typically responds well to chemotherapy regimens that include high-dose cytarabine. Some people benefit from adding targeted medicines such as gemtuzumab ozogamicin. Regular monitoring for minimal residual disease helps guide treatment decisions.
Acute myeloid leukemia with DEK::NUP214 fusion
This is a rare subtype caused by a fusion between DEK and NUP214, often associated with a chromosomal change called t(6;9). It can occur in children or adults.
People may have symptoms related to anemia, infection, and bleeding. Blood counts vary. Some people have high white blood cell counts, while others have low levels of multiple blood cell types, called pancytopenia.
Microscopically, the leukemia cells often show dysplasia, which means abnormal development of blood cells. This can make the bone marrow look similar to a myelodysplastic neoplasm in some cases. Leukemia cells commonly express CD13, CD33, CD34, and myeloperoxidase, and sometimes CD7 or CD15. FLT3 mutations are often present and may be associated with earlier relapse.
This subtype has a poor prognosis with frequent relapse. Allogeneic stem cell transplantation is often considered because it offers the best chance for longer-term survival. Some people may also receive therapies targeting FLT3 when that mutation is present.
Acute myeloid leukemia with RBM15::MRTFA fusion
This rare subtype mainly affects infants and young children and often shows megakaryocytic differentiation, meaning the leukemia cells resemble immature platelet-producing cells.
Typical findings include anemia, low platelets, and enlargement of the liver and spleen. Some infants develop leukemia outside the bone marrow, which can cause serious complications.
Microscopically, the leukemia cells are megakaryoblasts. They may have a deeply basophilic cytoplasm and sometimes small projections called blebs. Because bone marrow scarring can be present, obtaining a good aspirate may be challenging, and a biopsy is often needed. These cells usually express platelet markers such as CD41 and CD61 and are typically negative for myeloperoxidase.
Outcomes vary, with some studies showing moderate survival and others showing higher relapse rates. Treatment typically involves intensive chemotherapy, and close follow-up is essential.
Acute myeloid leukemia with BCR::ABL1 fusion
This is a rare subtype of acute myeloid leukemia characterized by the BCR::ABL1 fusion gene, the same fusion seen in chronic myeloid leukemia. In this subtype, however, the disease starts as acute myeloid leukemia without a preceding chronic phase.
Symptoms are typical of acute myeloid leukemia and include fatigue, infection, and bleeding. Some people have high white blood cell counts. Splenomegaly is uncommon compared with chronic myeloid leukaemia.
Microscopically, blasts are increased, often above 20 percent, and may appear as monocytic or very immature forms. The blasts commonly express CD34, CD13, and CD33. The diagnosis is confirmed by molecular testing for BCR::ABL1 or by identifying the t(9;22) translocation. Other mutations, such as RUNX1 or RAS pathway changes, may also be present.
This subtype has a poor prognosis if treated with chemotherapy alone. Tyrosine kinase inhibitors are usually needed, often in combination with chemotherapy. Allogeneic stem cell transplantation offers the best chance for long-term survival in many cases.
Acute myeloid leukemia with KMT2A rearrangement
This subtype is caused by changes in the KMT2A gene on chromosome 11. KMT2A can fuse with many different partner genes, and the specific partner can affect prognosis.
It can occur at any age but is especially common in infants and children. Many patients have high white blood cell counts and may develop leukemia outside the bone marrow, such as gum swelling, skin lesions, or enlargement of the liver or spleen.
Microscopically, the blasts often show monocytic or myelomonocytic differentiation. The cells commonly express CD33 and CD65, with variable CD34 and KIT. A marker called NG2 can be present. Additional mutations in RAS pathway genes or FLT3 may occur and influence response.
This subtype is often aggressive. Treatment usually includes intensive chemotherapy, and allogeneic stem cell transplantation may be recommended in higher-risk situations. Genetic testing is essential to guide risk assessment.
Acute myeloid leukemia with MECOM rearrangement
This is a rare and aggressive subtype caused by rearrangements involving the MECOM gene on chromosome 3, often through inv(3) or t(3;3). These changes lead to abnormal activity of the gene EVI1, disrupting normal blood cell development.
Patients may have anemia and abnormal platelet counts, which can be low or high. Enlargement of the liver and spleen is common.
Microscopically, dysplasia is often present in multiple blood cell lines. Megakaryocytes may look abnormal, sometimes with small, single-lobed, or bilobed nuclei. Blasts often express CD34, CD33, CD13, and KIT. Additional mutations, including RAS pathway or FLT3 changes, are common.
This subtype has a poor prognosis and often does not respond well to standard chemotherapy. Additional chromosomal changes, such as monosomy 7 or a complex karyotype, can worsen outcomes. Intensive treatment and consideration of stem cell transplantation are often discussed.
Acute myeloid leukemia with NUP98 rearrangement
This subtype involves rearrangements of the NUP98 gene on chromosome 11 with a variety of partner genes. It is more common in children.
Patients usually have typical acute myeloid leukemia symptoms. Blood counts may show increased blasts and sometimes high white blood cell counts.
Microscopically, blasts increase and may show monocytic, myelomonocytic, megakaryoblastic, or erythroid differentiation, depending on age and the fusion partner. The cells often express CD34, CD13, CD33, and myeloperoxidase, with additional markers such as CD41 or CD71 in some cases.
Because standard chromosome testing does not always detect these rearrangements, molecular tests such as FISH, RT-PCR, or RNA sequencing are often needed. This subtype is associated with a poor prognosis, especially when FLT3 internal tandem duplication is also present. Stem cell transplantation is usually recommended when remission is achieved.
Acute myeloid leukemia with NPM1 mutation
A mutation in the NPM1 gene defines this subtype. It is one of the most common forms of acute myeloid leukemia in adults. Patients may present with fatigue, bruising, bleeding, or infections. White blood cell counts are often high. Myeloid sarcoma can occur.
Microscopically, blasts often show myelomonocytic or monocytic features. A helpful clue is a cup-like shape of the nucleus in some blasts, especially if it is seen in more than 10 percent of cells. The blasts often express CD33, KIT, and myeloperoxidase, and many cases lack CD34. Molecular testing is needed to confirm the NPM1 mutation, most often in exon 12. Additional mutations such as FLT3, RAS, or DNMT3A are common and can affect risk.
This subtype often has a favorable prognosis, especially when FLT3 internal tandem duplication is absent or low. Monitoring for residual NPM1 mutation after treatment is essential because rising levels can signal relapse. Some people, especially older adults, are treated with newer combinations such as hypomethylating agents and venetoclax.
Acute myeloid leukemia with CEBPA mutation
This subtype is defined by specific mutations in the CEBPA gene, which helps control myeloid cell development. It can involve two mutations affecting both copies of the gene or a single mutation in a specific region called the bZIP region. In some cases, especially with specific patterns of CEBPA mutation, inheritance can occur, and genetic counselling may be recommended.
Patients often have high white blood cell counts and symptoms consistent with low-normal blood cell counts, such as fatigue, infections, and bleeding.
Microscopically, blasts are increased and may show some maturation. Dysplasia is common, especially in granulocytes and megakaryocytes. The blasts often express CD13, CD33, and CD34, and in many cases, they also express CD7.
This subtype is generally associated with a favorable prognosis, especially in the biallelic or bZIP-mutated groups. Many patients respond well to standard chemotherapy.
Acute myeloid leukemia, myelodysplasia-related
Myelodysplasia-related acute myeloid leukemia is characterized by specific genetic changes commonly observed in myelodysplastic syndromes or myelodysplastic myeloproliferative neoplasms. It can develop de novo or after a known history of these conditions.
Patients often have symptoms of severe bone marrow failure, including fatigue, infections, and bleeding due to low red cells, white cells, and platelets. Myeloid sarcoma can occur.
Microscopically, blasts are increased, and there is often multilineage dysplasia, meaning abnormal development in more than one blood cell line. Neutrophils may have abnormal nuclei, red blood cells may show defective maturation, and megakaryocytes may be small or abnormally shaped. Flow cytometry often shows blasts expressing CD34, KIT, and HLA-DR. Cytogenetic and molecular testing are crucial because mutations such as TP53, ASXL1, and SRSF2 are common.
This subtype generally has a poorer prognosis and lower remission rates than many other forms of acute myeloid leukemia. Treatment depends on overall health and genetic findings. TP53 mutations, especially with complex chromosome changes, are associated with worse outcomes.
Subtypes without specific molecular changes
Acute myeloid leukemia with minimal differentiation
This rare subtype shows very immature blasts that lack clear myeloid features under the microscope or with older chemical stains. The diagnosis relies on immunophenotyping, which tests what proteins the blasts express.
Patients have typical acute myeloid leukemia symptoms due to bone marrow failure. Most cases occur in adults. Some studies suggest that rearrangements involving the BCL11B gene may occur in a subset of cases, often alongside FLT3 internal tandem duplications and mutations in DNMT3A or TET2.
Microscopically, the bone marrow is often hypercellular and filled with sheets of blasts. The blasts are usually medium-sized and lack granules or Auer rods. By immunophenotyping, blasts commonly express CD13, CD33, CD117, CD34, and HLA-DR, but they are negative for myeloperoxidase. Chromosome changes and mutations in genes such as RUNX1, ASXL1, DNMT3A, and SRSF2 are common.
This subtype can be aggressive. Treatment is usually similar to that of other acute myeloid leukemia types. Molecular testing is essential because it may identify changes that influence risk or treatment options.
Acute myeloid leukemia with maturation
This subtype shows myeloid differentiation, meaning some leukemia cells begin to mature along the granulocyte pathway, but no defining genetic abnormality is found.
Patients typically have fatigue and anemia-related symptoms, low platelets, and low-normal white blood cell counts. Blood tests often show increased blasts. Monocytic cells make up less than 20 percent of bone marrow cells.
Microscopically, the bone marrow is hypercellular. Blasts may contain granules and sometimes Auer rods. At least 10 percent of marrow cells show granulocytic maturation, including promyelocytes, myelocytes, and mature neutrophils. The blasts typically express CD13, CD33, CD117, CD34, and HLA-DR, and are positive for myeloperoxidase. Markers of granulocytic maturation, such as CD11b, CD15, and CD65, are often present, while monocytic markers, such as CD14 and CD64, are uncommon.
Many cases have a normal karyotype, although chromosome gains and losses can occur. Mutations in genes such as ASXL1, RUNX1, and IDH2 are common, and these may influence prognosis.
Acute myeloid leukemia without maturation
This subtype is a form of acute myeloid leukemia where blasts grow but show little to no evidence of maturation.
Symptoms are related to bone marrow failure and include fatigue, bruising or bleeding, and infections. Blood tests often show blasts circulating in the blood.
Microscopically, the bone marrow is usually packed with blasts and shows very little granulocytic maturation. Some blasts may contain Auer rods. The blasts commonly express CD13, CD33, and CD117, and some express CD34 and HLA-DR. Markers of monocytes and mature granulocytes are usually absent or very limited. Genetic testing may show a normal karyotype in many cases, but mutations in genes such as DNMT3A, RUNX1, and FLT3 can be present and help guide risk assessment.
What happens after the diagnosis?
After acute myeloid leukemia is diagnosed, additional tests are often completed to fully understand the subtype, genetic features, and overall risk. These results help doctors decide on the most appropriate treatment plan. In many cases, treatment needs to start quickly because acute myeloid leukemia can progress rapidly.
Most patients are referred to a hematologist or leukemia specialist. Treatment often begins with chemotherapy, targeted therapy, or a combination of both. The exact treatment depends on the leukemia subtype, genetic findings, the patient’s age, and overall health. Some people may be hospitalized, especially during the first phase of therapy, because close monitoring is needed.
During and after treatment, blood tests and, sometimes, repeated bone marrow biopsies are used to assess how well the leukemia is responding. Doctors look for a decrease or disappearance of blasts and for recovery of normal blood cell production. Molecular tests may also be used to detect very small amounts of remaining leukemia, called minimal residual disease, which can help guide further treatment decisions.
In some cases, especially for higher-risk forms of acute myeloid leukemia, an allogeneic stem cell transplant may be recommended once remission is achieved. Your care team will discuss the benefits and risks of each option and help guide decisions based on your individual situation.
Questions for your doctor
- What subtype of acute myeloid leukemia do I have?
- What genetic or molecular changes were found in my leukemia cells?
- How do these results affect my treatment options and prognosis?
- Do I need treatment right away, and what does that treatment involve?
- Will I need to stay in the hospital during treatment?
- How will you know if the treatment is working?
- Will my bone marrow or blood be tested again after treatment?
- Am I a candidate for stem cell transplantation?
- What side effects should I expect from treatment?
- Who should I contact if I develop a fever, bleeding, or new symptoms?
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