Acute Myeloid Leukemia (AML): Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and David Li MD
April 14, 2026

Acute myeloid leukemia (AML) 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 can no longer produce enough normal red blood cells, white blood cells, and platelets. This leads to anemia, infections, and bleeding. Acute myeloid leukemia is called “acute” because it can worsen quickly — sometimes over days to weeks — if it is not treated. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

What are the symptoms of acute myeloid leukemia?

The symptoms of acute myeloid leukemia develop because the bone marrow can no longer make enough normal blood cells. As leukemia blasts build up, they crowd out healthy cells and cause low blood counts.

Low red blood cells — a condition called anemia — can cause fatigue, weakness, shortness of breath, dizziness, and pale skin. Low platelets can lead to easy bruising, frequent nosebleeds, bleeding gums, prolonged bleeding from minor cuts, or tiny red or purple spots on the skin caused by bleeding just under the surface. Low or poorly functioning white blood cells increase the risk of infection, which may show up as frequent fevers or infections that are hard to clear.

Some people experience bone or joint pain due to the crowding of leukemia cells in the marrow. Swollen lymph nodes or enlargement of the liver or spleen can also occur, sometimes causing a feeling of fullness or discomfort in the abdomen. Symptoms often develop and worsen quickly, which is why evaluation and treatment tend to begin soon after diagnosis.

What causes acute myeloid leukemia?

Acute myeloid leukemia is caused by acquired genetic changes — changes that are not inherited but happen over a person’s lifetime 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 begin to multiply uncontrollably and fail to develop into normal, functioning blood cells.

In many cases, these changes involve specific chromosomal rearrangements, gene fusions, or mutations. 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 clear reason why these changes occur. However, certain factors can increase the risk, including prior chemotherapy or radiation therapy for another cancer, exposure to high levels of radiation or certain chemicals such as benzene, and pre-existing blood disorders such as myelodysplastic syndrome 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 the diagnosis made?

The diagnosis of acute myeloid leukemia is made by examining blood and bone marrow samples, combined with special laboratory tests. A complete blood count often reveals low red blood cell, platelet, or white blood cell counts, and blasts may be visible on a blood smear. To confirm the diagnosis, a bone marrow biopsy and aspiration are performed — a procedure in which a small sample of bone marrow is removed from the hip bone using a needle, usually under local anesthesia. The pathologist examines the marrow under the microscope, counting the percentage of blasts and looking for features that suggest a specific subtype. In acute myeloid leukemia, blasts typically account for 20% or more of the cells in the marrow or blood. Flow cytometry is then used to identify which proteins the blasts express, confirming their myeloid origin and distinguishing acute myeloid leukemia from other blood cancers, such as acute lymphoblastic leukemia. Genetic and molecular tests — including chromosome analysis, FISH, PCR, and next-generation sequencing — identify the specific gene changes that define the leukemia subtype and guide risk assessment and treatment.

What are the subtypes of acute myeloid leukemia?

Pathologists classify acute myeloid leukemia into subtypes based on the specific molecular or genetic changes found in the leukemia cells. Knowing the subtype matters because it helps estimate prognosis and select the right treatment. The most important subtypes are summarized below. Because each subtype has unique features and treatment implications, future dedicated articles will cover each one in greater depth.

Acute promyelocytic leukemia (APL) with PML::RARA fusion

This subtype is caused by a fusion of the PML and RARA genes, which blocks normal blood cell development and leads to a buildup of abnormal cells called promyelocytes. A major concern is a dangerous clotting disorder called disseminated intravascular coagulation, which can cause serious bleeding if not treated quickly. With modern treatment using all-trans retinoic acid and arsenic trioxide, this subtype has an excellent prognosis and is among the most curable forms of leukemia.

AML with RUNX1::RUNX1T1 fusion

Caused by a fusion of the RUNX1 and RUNX1T1 genes, this subtype typically responds well to intensive chemotherapy, including high-dose cytarabine. Additional mutations in the KIT gene can affect prognosis.

AML with CBFB::MYH11 fusion

This subtype involves a fusion of CBFB and MYH11 — often detected as inv(16) or t(16;16) on chromosome testing — and is associated with abnormal eosinophils in the blood and bone marrow. It generally responds well to chemotherapy that includes high-dose cytarabine.

AML with KMT2A rearrangement

Caused by rearrangements of the KMT2A gene, this subtype is especially common in infants and children and can involve many different partner genes. It is often aggressive, and stem cell transplantation may be recommended.

AML with NPM1 mutation

One of the most common subtypes in adults is defined by a mutation in the NPM1 gene. It often has a favorable prognosis when FLT3 internal tandem duplication is absent or at a low level. Monitoring for residual NPM1 mutation after treatment is essential.

AML with CEBPA mutation

Defined by mutations in the CEBPA gene, which controls myeloid cell development. Biallelic or bZIP-region mutations are associated with a favorable prognosis. Some cases may be inherited, and genetic counseling may be recommended.

AML with BCR::ABL1 fusion

A rare subtype involving the same BCR::ABL1 fusion seen in chronic myeloid leukemia, but presenting as acute leukemia without a preceding chronic phase. Tyrosine kinase inhibitors are needed alongside chemotherapy, and stem cell transplantation is often recommended.

AML with other fusions (DEK::NUP214, RBM15::MRTFA, MECOM rearrangement, NUP98 rearrangement)

Specific gene fusions or rearrangements define several other rare subtypes. Many of these carry a poor prognosis and are treated with intensive chemotherapy and stem cell transplantation when possible.

AML, myelodysplasia-related

This subtype arises from genetic changes commonly seen in myelodysplastic syndrome and may develop in people with a prior history of that condition. It is often associated with a poorer prognosis and may harbor mutations in TP53, ASXL1, or SRSF2.

AML without a specific defining alteration

When no defining genetic change is identified, the subtype is classified based on how the leukemia cells look under the microscope and what proteins they express. These include AML with minimal differentiation, AML without maturation, and AML with maturation. Molecular testing remains important because mutations identified in these cases can affect risk and treatment options.

Risk stratification in acute myeloid leukemia

Once the genetic and molecular results are available, your care team will assign your leukemia to a risk group. Risk stratification — the process of placing a patient into a favorable, intermediate, or adverse risk category — is one of the most important steps after diagnosis because it directly guides major treatment decisions, especially whether a stem cell transplant should be considered.

Risk groups are based on European LeukemiaNet (ELN) 2022 guidelines, which use specific genetic and molecular findings to estimate the likelihood of long-term remission with standard treatment:

Favorable risk — Includes subtypes such as APL with PML::RARA fusion, AML with RUNX1::RUNX1T1 or CBFB::MYH11 fusions, and AML with NPM1 mutation (without high-level FLT3-ITD) or biallelic CEBPA mutation. People in this group generally respond well to chemotherapy, and stem cell transplantation in first remission is not usually recommended.
Intermediate risk — Includes AML with NPM1 mutation and high-level FLT3-ITD, AML with low-level FLT3-ITD without NPM1 mutation, and cases with a normal karyotype without other defining features. The benefit of transplantation in first remission is considered on an individual basis.
Adverse risk — Includes AML with TP53 mutation, MECOM rearrangement, complex karyotype, monosomy 7, or certain other high-risk changes. People in this group have a higher risk of relapse with standard chemotherapy, and stem cell transplantation in first remission is generally recommended when possible.

Risk group is not the only factor in treatment planning. Age, overall health, and whether the person is a candidate for intensive therapy or transplantation are also considered. Your care team will explain your specific risk group and what it means for your treatment plan.

Biomarker and molecular testing

Molecular testing identifies genetic changes in leukemia cells that help define the subtype, estimate the risk of relapse, and select targeted treatments. Some of these changes — such as PML::RARA, RUNX1::RUNX1T1, and CBFB::MYH11 fusions — are primarily diagnostic, meaning they define the subtype and are covered in the subtypes section above. Others are directly actionable, meaning specific drugs exist that target them. The most important therapeutic targets are described below.

FLT3 mutation

The FLT3 gene encodes a protein that helps blood stem cells grow and survive. Two types of FLT3 mutations occur in acute myeloid leukemia: internal tandem duplication (FLT3-ITD) and point mutation (FLT3-TKD). FLT3-ITD involves an extra copy of a segment of the gene inserted into the gene, causing the FLT3 protein to be constantly expressed, driving uncontrolled blast growth. FLT3-ITD is found in approximately 25–30% of adults with acute myeloid leukemia and is associated with a higher risk of relapse when present at high levels.

Two FLT3 inhibitors are approved for the treatment of acute myeloid leukemia. Midostaurin is used alongside standard induction chemotherapy in newly diagnosed FLT3-mutated acute myeloid leukemia; adding midostaurin to chemotherapy improves overall survival compared to chemotherapy alone. Quizartinib and gilteritinib are approved for relapsed or refractory FLT3-ITD-positive disease; gilteritinib is also used as a single agent in relapsed FLT3-mutated acute myeloid leukemia and has shown response rates of approximately 20–25% in heavily pretreated patients. FLT3 testing is performed at diagnosis in all patients with acute myeloid leukemia.

IDH1 and IDH2 mutations

The IDH1 and IDH2 genes normally produce enzymes involved in cell energy metabolism. When mutated in leukemia, these enzymes produce an abnormal substance called 2-hydroxyglutarate that blocks blood cell maturation, contributing to blast accumulation. IDH1 mutations occur in approximately 6–10% of adults with acute myeloid leukemia; IDH2 mutations occur in approximately 8–15%.

Targeted inhibitors are approved for both mutations. Ivosidenib targets IDH1 and is approved for newly diagnosed IDH1-mutated acute myeloid leukemia in patients who are not candidates for intensive chemotherapy (often used in combination with azacitidine), as well as for relapsed or refractory IDH1-mutated disease. Enasidenib targets IDH2 and is approved for relapsed or refractory IDH2-mutated acute myeloid leukemia, with complete remission rates of approximately 20% as a single agent. Olutasidenib is a newer IDH1 inhibitor also approved for relapsed or refractory IDH1-mutated disease. IDH1 and IDH2 testing is routinely performed at diagnosis.

NPM1 mutation

The NPM1 gene normally helps regulate cell growth and transports proteins into and out of the cell nucleus. Mutations in NPM1 cause the NPM1 protein to move to the wrong place inside the cell, disrupting normal blood cell development. NPM1 mutations are found in approximately 25–35% of adults with acute myeloid leukemia and are one of the most important markers used to monitor residual disease after treatment. Rising levels of NPM1 mutation detected in the blood or bone marrow after treatment are a strong early signal of relapse, often before blasts reappear under the microscope.

TP53 mutation

The TP53 gene normally acts as a brake on uncontrolled cell growth by detecting DNA damage and triggering cell death. When TP53 is mutated in acute myeloid leukemia — which occurs in approximately 5–10% of cases — this brake is lost, and leukemia cells become more resistant to chemotherapy-induced cell death. TP53 mutations place patients in the adverse ELN risk group and are associated with lower remission rates and shorter survival with standard treatment. Eprenetapopt (APR-246) is an investigational drug that reactivates mutant p53 protein and has shown activity in TP53-mutated acute myeloid leukemia in clinical trials, though it is not yet broadly approved. Patients with TP53-mutated acute myeloid leukemia are often considered for clinical trials.

BCL2 — venetoclax

BCL2 is a protein that prevents leukemia cells from dying — it acts as a survival signal that keeps blasts alive even when they should undergo programmed cell death. Venetoclax is a drug that blocks BCL2, removing this survival signal and allowing leukemia cells to die. Venetoclax is not used as a single agent in acute myeloid leukemia but is highly effective in combination with hypomethylating agents (azacitidine or decitabine). The combination of venetoclax plus azacitidine is now a standard first-line treatment for adults aged 75 and older or those who cannot tolerate intensive chemotherapy, with complete remission rates of approximately 37% and a median overall survival of approximately 14 months — a substantial improvement over prior standards of care for this population. Venetoclax-based combinations are also used in the relapsed setting.

CD33 — gemtuzumab ozogamicin

CD33 is a protein found on the surface of most acute myeloid leukemia blasts. Gemtuzumab ozogamicin is an antibody-drug conjugate — an antibody that seeks out CD33-positive leukemia cells and delivers a toxic chemotherapy payload directly into them. It is approved for CD33-positive acute myeloid leukemia and is particularly beneficial in favorable-risk disease (especially AML with RUNX1::RUNX1T1 or CBFB::MYH11 fusions), where adding it to standard chemotherapy has improved outcomes. CD33 expression is typically confirmed by flow cytometry at diagnosis.

For more information about biomarkers and molecular testing in blood cancers, visit the Biomarkers and Genetic Testing section.

Minimal residual disease (MRD)

Minimal residual disease — often abbreviated MRD — refers to very small numbers of leukemia cells that may remain in the body after treatment, at levels too low to be detected by standard microscopic examination of the bone marrow. Even when a bone marrow biopsy shows no visible blasts, sensitive molecular tests can detect residual leukemia cells at concentrations as low as 1 in 10,000 or 1 in 100,000 cells.

MRD is measured using highly sensitive techniques. Flow cytometry can detect abnormal blast populations at low levels. For subtypes with specific molecular markers — such as NPM1 mutation or PML::RARA fusion — PCR-based tests can quantify the amount of leukemia-specific genetic material remaining in the blood or bone marrow. Next-generation sequencing can also detect low-level mutations in some cases.

MRD results are reported as either MRD negative (no residual leukemia detected below a defined threshold) or MRD positive (detectable residual leukemia). These results matter for several reasons. Achieving MRD negativity after initial treatment is associated with a lower risk of relapse and longer survival in most subtypes. Conversely, rising MRD levels after initial clearance — sometimes called molecular relapse — can predict that the leukemia is returning, often weeks before blasts reappear under the microscope. This early warning can allow treatment to be adjusted before full relapse occurs. In some subtypes, such as APL with PML::RARA fusion, MRD monitoring by PCR is a standard part of follow-up care, and a positive result after consolidation therapy prompts treatment even in the absence of symptoms.

MRD is an evolving area of acute myeloid leukemia management, and testing intervals and the response to positive results vary by subtype and treatment protocol. Your care team will explain how MRD will be monitored in your situation.

What is remission, and how is it assessed?

Remission in acute myeloid leukemia means that treatment has reduced the leukemia to a level that standard tests cannot detect, and the bone marrow has recovered enough to produce normal blood cells again. Remission is not the same as a cure — it means the leukemia is no longer detectable, but the risk of it returning depends on the subtype and risk group.

Doctors use specific criteria to define remission. The most common is complete remission, which requires all of the following: fewer than 5 percent blasts in the bone marrow on microscopic examination, recovery of normal blood cell counts (absolute neutrophil count above 1.0 × 10⁹/L and platelets above 100 × 10⁹/L), and no detectable leukemia outside the bone marrow. Complete remission is assessed by a repeat bone marrow biopsy, usually after one or two cycles of treatment.

Beyond standard complete remission, doctors increasingly use more sensitive measures. Cytogenetic remission means that an abnormal chromosome finding — such as the t(15;17) translocation in APL — is no longer detectable by chromosome analysis. Molecular remission (also called MRD negativity) means that even sensitive molecular tests cannot detect residual leukemia. Achieving deeper remission is associated with a lower risk of relapse. Your pathology report after treatment may describe the bone marrow as “in remission,” “MRD negative,” or may report a specific MRD value — each of these has important implications for ongoing treatment decisions.

What is the prognosis?

Prognosis in acute myeloid leukemia varies widely depending on the subtype, risk group, age, and overall health. Overall, approximately 40–45% of adults under 60 who receive intensive chemotherapy achieve long-term remission, while outcomes are more modest in older adults or those who cannot tolerate intensive treatment.

Subtype and risk group have the greatest influence on outcome:

Acute promyelocytic leukemia (APL) — The most favorable subtype. With all-trans retinoic acid and arsenic trioxide-based therapy, long-term remission rates exceed 90% in low- and intermediate-risk cases, making this one of the most curable leukemias. Early identification and treatment are critical because the associated clotting disorder can be life-threatening before treatment begins.
Core-binding factor AML (RUNX1::RUNX1T1 and CBFB::MYH11 fusions) — Favorable risk. Five-year overall survival is approximately 60–70% with intensive chemotherapy. Additional KIT mutations can worsen outcomes in this group.
NPM1-mutated AML (without high-level FLT3-ITD) — Favorable risk. Five-year overall survival is approximately 50–60% with standard therapy.
Intermediate-risk AML — Outcomes are variable. Five-year overall survival is generally 30–50%, and transplantation decisions are individualized.
Adverse-risk AML (including TP53 mutation, complex karyotype, MECOM rearrangement) — Five-year overall survival is generally below 20% with standard treatment. Stem cell transplantation improves outcomes in eligible patients, but many in this group have a disease that is difficult to keep in remission.
AML in older adults — Age significantly affects both response to treatment and ability to tolerate intensive therapy. Adults over 75 or those with significant other medical conditions are typically treated with lower-intensity regimens such as venetoclax plus azacitidine rather than intensive induction chemotherapy.

Factors associated with a worse prognosis include adverse-risk genetic changes, older age, poor performance status, secondary AML arising from a prior blood disorder such as myelodysplastic syndrome, and therapy-related AML following prior chemotherapy or radiation. Achieving MRD negativity after treatment is one of the strongest indicators of a favorable outcome, regardless of risk group.

Prognosis is best discussed with your hematologist, who can integrate all of these factors — subtype, risk group, age, overall health, and treatment response — to give you the most accurate and individualized picture.

What happens after the diagnosis?

After acute myeloid leukemia is diagnosed, additional molecular and genetic test results are usually needed to finalize the subtype and risk group. Because acute myeloid leukemia can progress rapidly, treatment typically begins quickly — often within days of diagnosis. Most patients are referred to a hematologist or leukemia specialist and are managed at a center with experience treating blood cancers.

For people who can tolerate intensive treatment, the first step is induction chemotherapy — a combination of cytarabine and an anthracycline such as daunorubicin or idarubicin, often referred to as “7+3.” For FLT3-mutated disease, midostaurin is added to this regimen. The goal of induction is to achieve complete remission, which is assessed by a repeat bone marrow biopsy after treatment. Induction is usually given in a hospital because close monitoring of blood counts and management of infection are required.

Once remission is achieved, consolidation therapy is given to reduce the risk of relapse. For favorable-risk disease, consolidation involves cycles of high-dose cytarabine chemotherapy. For intermediate- and high-risk disease, allogeneic stem cell transplantation — a procedure in which healthy donor blood stem cells are infused after intensive conditioning to replace the diseased bone marrow — is often recommended in first remission. For patients who cannot tolerate intensive induction, the combination of venetoclax with azacitidine or decitabine is the standard approach. IDH1- or IDH2-targeted agents may be incorporated into treatment for patients with those mutations.

During and after treatment, blood counts and bone marrow biopsies are used to monitor response, and molecular tests are used to track MRD. Your care team will discuss the treatment plan, the expected timeline, and what to watch for at each stage.

Questions to ask your doctor

What subtype of acute myeloid leukemia do I have, and what genetic or molecular changes were found?
What risk group am I in — favorable, intermediate, or adverse — and what does that mean for my treatment?
Do I have a FLT3, IDH1, IDH2, NPM1, TP53, or CEBPA mutation, and does that change my treatment options?
Will I receive targeted therapy alongside chemotherapy, or am I a candidate for lower-intensity treatment such as venetoclax plus azacitidine?
Do I need treatment right away, and will I need to be admitted to the hospital?
How will you know if the treatment is working, and when will my bone marrow be re-examined?
Will my leukemia be tested for minimal residual disease (MRD), and how will those results affect my treatment?
Am I a candidate for a stem cell transplant, and at what point would that be recommended?
Could my leukemia or any of the mutations found be related to an inherited condition that my family members should know about?
What side effects should I expect from treatment, and who should I contact if I develop a fever, bleeding, or new symptoms?
Are there clinical trials available for my subtype or risk group that I should consider?
What does remission mean in my case, and what is the plan if the leukemia comes back?