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Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy caused by uncontrolled proliferation of abnormal immature myeloid precursor cells (myeloblasts) in the bone marrow. The abnormal cells suppress normal blood-cell production and may infiltrate other tissues

Also called

Acute Myelogenous Leukemia

ICD-10

C92.0

Specialty

Hematology

Onset

Acute

Reviewed

August 2026

On This Page

Overview

Acute Myeloid Leukemia (AML) develops from malignant transformation of myeloid precursor cells, causing rapid accumulation of blasts in the bone marrow. This leads to anemia, neutropenia, and thrombocytopenia, producing fatigue, infections, and bleeding. Acute Myeloid Leukemia (AML) can occur at any age but is particularly common in older adults

Etiology & Risk Factors

The exact cause is often unknown. Acute Myeloid Leukemia (AML) results from acquired genetic and molecular abnormalities that cause:

  • Uncontrolled proliferation
  • Impaired differentiation
  • Accumulation of immature myeloid blasts

-Risk Factors

  • Increasing age
  • Previous chemotherapy
  • Previous radiotherapy
  • Benzene exposure
  • Smoking
  • Myelodysplastic Syndrome (MDS)
  • Myeloproliferative neoplasms
  • Previous aplastic anemia
  • Down syndrome and other genetic disorders
  • Previous treatment with topoisomerase II inhibitors

Pathophysiology

Genetic mutations in a hematopoietic stem/progenitor cell → abnormal myeloid precursor proliferation and impaired differentiation → accumulation of myeloblasts in the bone marrow → suppression of normal hematopoiesis → anemia, neutropenia, and thrombocytopenia → infiltration of peripheral tissues such as skin, gums, spleen, and CNS in some patients.

Clinical Presentation

Symptoms

  • Fatigue

  • Weakness

  • Pallor

  • Fever

  • Recurrent infections

  • Easy bruising

  • Bleeding

  • Bone pain

  • Weight loss

  • Shortness of breath

Signs

  • Pallor

  • Fever

  • Petechiae

  • Ecchymoses

  • Lymphadenopathy

  • Hepatosplenomegaly

  • Gingival hypertrophy

  • Skin infiltration

  • Bone tenderness

History Taking

-Ask about:

  • Fatigue
  • Fever
  • Recurrent infections
  • Bleeding
  • Easy bruising
  • Bone pain
  • Weight loss
  • Night sweats
  • Shortness of breath
  • Previous chemotherapy or radiotherapy
  • Occupational exposure to benzene
  • Previous MDS or other hematologic disorders
  • Family history
  • Neurological symptoms

Physical Examination

-General Examination

Look for:

  • Pallor

  • Fever

  • Weight loss

  • Petechiae

  • Ecchymoses

  • Signs of infection

-Lymph Node Examination

Assess for:

  • Cervical

  • Axillary

  • Inguinal lymphadenopathy

-Abdominal Examination

Look for:

  • Hepatomegaly

  • Splenomegaly

-Oral Examination

Look for:

  • Gingival hypertrophy

  • Mucosal bleeding

  • Oral infections

-Skin Examination

Assess for:

  • Petechiae

  • Ecchymoses

  • Leukemic skin infiltration

Investigations

Complete Blood Count (CBC)

May show:

  • Anemia

  • Thrombocytopenia

  • Neutropenia

  • Leukocytosis, normal WBC, or leukopenia

  • Circulating blasts

Peripheral Blood Film

May show:

  • Myeloblasts

  • Auer rods

  • Anemia

  • Thrombocytopenia

  • Abnormal WBC count

Important Finding

Auer rods strongly support myeloid differentiation.

 

Bone Marrow Aspiration & Biopsy — Gold Standard

Typical findings:

  • Increased myeloblasts

  • Usually ≥20% blasts in the bone marrow or peripheral blood

Some genetically defined AML entities can be diagnosed without meeting the 20% blast threshold.

Flow Cytometry

Used to establish myeloid lineage.

Common markers include:

  • CD13

  • CD33

  • CD117

  • MPO

  • HLA-DR

  • CD34 in many cases

Cytogenetic & Molecular Testing

Important abnormalities include:

  • t(8;21) / RUNX1-RUNX1T1

  • inv(16) / CBFB-MYH11

  • PML-RARA

  • FLT3 mutations

  • NPM1 mutations

  • CEBPA mutations

  • TP53 abnormalities

These findings are essential for classification, prognosis, and treatment selection.

Coagulation Studies

Especially important when Acute Promyelocytic Leukemia (APL) is suspected:

  • PT

  • aPTT

  • Fibrinogen

  • D-dimer

Additional Investigations

  • Urea and electrolytes

  • Creatinine

  • Liver function tests

  • LDH

  • Uric acid

  • Blood cultures if febrile

  • Chest imaging if infection suspected

  • Baseline cardiac assessment before anthracyclines

Diagnosis

Diagnosis is based on:

  • CBC and peripheral blood film
  • Bone marrow examination
  • Blast percentage
  • Flow cytometry
  • Cytogenetic and molecular studies

Classification identifies the specific genetic and molecular subtype of Acute Myeloid Leukemia (AML).

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Management

-Initial Management

Treatment depends on:

  • Age

  • Fitness

  • Cytogenetic/molecular risk

  • Comorbidities

  • AML subtype

Fit Patients

-Intensive induction chemotherapy may include:

  • Cytarabine

  • An anthracycline such as daunorubicin or idarubicin

This is commonly known as “7+3” induction.

Targeted agents may be added depending on molecular abnormalities.

-Consolidation

After achieving remission:

  • High-dose cytarabine in selected patients

  • Allogeneic hematopoietic stem cell transplantation for appropriate intermediate/high-risk patients

-Older / Unfit Patients

Common approaches include:

  • Azacitidine + venetoclax

  • Other lower-intensity or targeted regimens depending on molecular findings and patient fitness

-Acute Promyelocytic Leukemia (APL)

APL is a medical emergency because of severe coagulopathy.

Treatment commonly involves:

  • All-trans retinoic acid (ATRA)

  • Arsenic trioxide

  • ± chemotherapy depending on risk

ATRA should be started immediately when APL is strongly suspected.

Supportive Care

  • Red blood cell transfusions

  • Platelet transfusions

  • Prompt treatment of infections

  • Tumor lysis syndrome prevention

  • Antimicrobial prophylaxis when appropriate

  • Management of chemotherapy complications

Complications

  • Severe anemia
  • Severe infections
  • Bleeding
  • Disseminated intravascular coagulation, especially in APL
  • Tumor lysis syndrome
  • Leukostasis
  • CNS involvement
  • Organ infiltration
  • Treatment-related complications
  • Relapse

Prognosis

Prognosis varies considerably according to age, overall fitness, cytogenetic abnormalities, molecular mutations, treatment response, and measurable residual disease (MRD). Some genetically favorable forms have excellent outcomes, while adverse-risk Acute Myeloid Leukemia (AML) may require stem cell transplantation and has a higher relapse risk.

Key Points / Clinical Pearls

  • Acute Myeloid Leukemia (AML) is a malignancy of immature myeloid cells.
  • It is more common in older adults.
  • Common presentation: anemia + infection + bleeding.
  • Peripheral blood may show myeloblasts and Auer rods.
  • Bone marrow examination is essential for diagnosis.
  • Flow cytometry establishes myeloid lineage.
  • Cytogenetic and molecular testing guides prognosis and treatment.
  • PML-RARA identifies Acute Promyelocytic Leukemia (APL).
  • Suspected APL requires immediate ATRA.
  • Fit patients may receive intensive induction such as 7+3.
  • Azacitidine + venetoclax is commonly used in many older/unfit patients.
  • Allogeneic stem cell transplantation is used in selected patients at significant risk of relapse.