Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Clinical presentation consisting of fatigue, bleeding, fever, and infection is related to anemia, thrombocytopenia, and a lack of functional WBCs. The onset of symptoms takes days to weeks. Additional findings in AML may include gingival hypertrophy and skin infiltration (leukemia cutis). Diagnosis is via peripheral blood smear and bone-marrow biopsy examination (shows myeloblasts). The precursor cells contain Auer rods. Immunophenotyping, histochemistry, and genetic analysis all aid in identifying and guiding the treatment of AML. Management is chemotherapy administered in phases (induction, consolidation, and maintenance) based on subtypes. Prognosis varies according to the age of onset and type of leukemia.

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Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the pathological proliferation of myeloid precursor cells in the bone marrow and subsequent displacement of other blood cell precursors.


The World Health Organization (WHO) classification system is based on multiple factors, including morphology, genetics, and clinical features:

  • AML with recurrent genetic abnormalities
  • AML with myelodysplasia-related changes 
  • Therapy-related AML and myelodysplastic syndrome
  • AML not otherwise specified
  • Myeloid sarcoma
  • Myeloid proliferations related to Down syndrome

Epidemiology and Etiology


  • AML is mostly seen in adults:
    • Mean age of onset: 65 years old
    • United States incidence rate: 20 cases per 100,000 in patients > 65 years of age
  • Seen in children, but less frequently (accounts for 10% of acute childhood leukemias) 
  • Accounts for 1% of adult cancer-related deaths in the United States
  • Slightly higher incidence in men and nonHispanic whites


  • May be primary (new malignancy) or secondary (occurring after chemotherapy or radiation therapy for a different type of cancer)
  • Increased risk in the following conditions:
    • Down syndrome
    • Fanconi anemia
    • Bloom syndrome
  • Ionizing radiation
  • Chemical exposure (e.g., benzene, alkylating agents for another cancer)
  • Preleukemic hematopoietic disorders:
    • Myelodysplastic syndromes
    • Aplastic anemia
    • Myeloproliferative disorders



Hematopoiesis begins with a hematopoietic stem cell, which is prompted to divide and differentiate with appropriate chemical stimuli (hemopoietic growth factors).

  • Lymphoid stem cells give rise to lymphocytes:
    • T cell
    • B cell
    • Natural killer (NK) cells
  • Myeloid stem cells differentiate into platelets, erythrocytes, granulocytes (neutrophils, basophils, eosinophils), and monocytes:
    • IL-3 stimulates the differentiation of multipotent hematopoietic stem cells into myeloid progenitor cells.
    • Granulocyte-macrophage colony-stimulating factor (GM-CSF) → differentiation from myeloid progenitors to granulocytes (neutrophils) and monocytes 
    • IL-5 → differentiation to eosinophils
    • Thrombopoietin (TPO) → differentiation to thrombocytes (platelets)
    • EPO → differentiation to erythrocytes (RBCs)
Bone marrow hematopoiesis

Bone-marrow hematopoiesis: proliferation and differentiation of the formed elements of blood.
CFU-GEMM: colony-forming unit–granulocyte, erythrocyte, monocyte, megakaryocyte
CFU-GM: colony-forming unit–granulocyte-macrophage
GM-CSF: granulocyte-macrophage colony-stimulating factor
M-CSF: macrophage colony-stimulating factor
G-CSF: granulocyte colony-stimulating factor
NK: natural killer
TPO: thrombopoietin

Image by Lecturio. License: CC BY-NC-SA 4.0


  • In AML, myeloid differentiation is impeded by mutations, which affect the development of precursor cells.
  • AML is associated with specific chromosomal alterations such as:
    • Translocation: t(8;21) disruption of the RUNX1 gene, which is required for normal hematopoiesis
    • Inversion: inv(16) disruption of the CBFB gene
    • Deletion: del(5q)
  • Abnormal cells proliferate but cannot differentiate into mature blood cells:
    • Monoclonal leukemic cells occupy the bone-marrow space and suppress normal hematopoiesis → leukopenia, thrombocytopenia, and anemia
    • Dysfunctional and immature blasts enter the bloodstream and infiltrate other organs.

Clinical Presentation

General clinical features

  • Some patients are asymptomatic and present with only laboratory irregularities. 
  • Signs and symptoms related to hematologic abnormalities:
    • Anemia:
      • Fatigue, tachycardia
      • Pallor
    • Thrombocytopenia:
      • Bleeding
      • Petechiae
      • Ecchymoses
    • Neutropenia:
      • Fever
      • Recurrent infections
    • Leukostasis or hyperleukocytosis:
      • AML with neurologic manifestations and respiratory problems or myeloblasts > 50,000/μL, OR
      • AML and myeloblasts > 100,000/μL
  • Additional signs of AML:
    • Leukemia cutis (purple/gray-blue papular or nodular skin lesions) and myeloid sarcoma: represent leukemic skin infiltration
    • Sweet syndrome: tender nodules and plaques
    • Gingival hypertrophy: infiltration seen in acute monocytic leukemia and acute myelomonocytic leukemia 
    • Bleeding or bruising: signs of DIC in acute promyelocytic leukemia
    • Visual field changes, papilledema, retinal infiltrates, and cranial nerve palsy: seen in AML seeding the CNS 
  • Organomegaly (hepatomegaly and splenomegaly) seen in approximately 10% of patients
  • Lymphadenopathy: rare

Acute lymphoblastic leukemia (ALL) versus acute myeloid leukemia

Table: ALL versus AML
PopulationMore common in childrenMore common in adults
Common characteristics
  • Symptoms of anemia, thrombocytopenia, neutropenia (from depressed marrow function)
  • Abrupt onset (days to weeks)
  • CNS involvement
Clinical findings
  • Hepato- and splenomegaly
  • Lymphadenopathy
  • Bone pain more common
  • Can affect testes
  • Can have mediastinal mass
  • Organomegaly less frequent
  • Lymphadenopathy rare
  • Leukemia cutis
  • Gingival hypertrophy
  • DIC


Diagnostic findings

  • CBC with differential:
    • Anemia, thrombocytopenia
    • Varying WBCs
  • Peripheral smear: 
    • Myeloblasts:
      • More voluminous cytoplasm
      • Large nuclei
      • Prominent nucleoli
      • Delicate/fine nuclear chromatin
      • Peroxidase-positive azurophilic granules 
    • Auer rods:
      • Pink/red, needle- or rod-like or granular structures in the cytoplasm
      • Seen in many AML forms especially in t(15;17)-acute promyelocytic leukemia
      • Rich in lysosomal enzymes/myeloperoxidase (MPO) 
    • Most myeloblasts are positive for MPO, which confirms myeloid lineage, but some AML are negative.
  • Bone-marrow examination: 
    • Usually hypercellular: > 20% myeloblasts (some forms are exceptional)
    • A dry tap indicates extensive fibrosis or hypercellular (packed) bone marrow.
  • Cytochemistry:
    • Sudan Black B: positive
    • MPO: positive 
    • TdT: negative
  • Immunophenotyping: common antigens include CD13, CD33, CD117, HLA-DR.
  • Genetic analysis: identifies mutations
AML bone marrow findings of Auer rods

Acute myeloid leukemia (AML): bone-marrow findings of Auer rods (pink, needle-like structures in the cytoplasm) in a myeloblast

Image: “Auer Rods in Leukemic Blast” by Ed Uthman. License: CC BY 2.0

Acute lymphoblastic leukemia versus acute myeloid leukemia

Table: ALL versus AML
Laboratory findingsAnemia, thrombocytopenia, varying WBCs
Peripheral smear or bone-marrow examination (morphology)Lymphoblasts:
  • Large nuclei
  • Condensed chromatin
  • Inconspicuous nucleoli
  • Scant basophilic cytoplasm
  • Delicate nuclear chromatin
  • Prominent nucleoli (2–4)
  • More voluminous cytoplasm
  • Fine azurophilic-cytoplasmic granules
  • Auer rods
  • PAS: positive
  • MPO: negative
  • TdT: positive
  • PAS: negative
  • Sudan Black B: positive
  • MPO: positive
  • TdT: negative
  • B-ALL/LBL: CD10, CD19, CD20, CD24, cytoplasmic CD22, and CD-79a
  • T-ALL/LBL: CD2–8
CD13, CD33, CD117, HLA-DR



Chemotherapy requires pretreatment evaluation, including patient goals and preferences, comorbidities, physical functioning, and prognostic factors related to AML type.

  • Intensive remission induction:
    • Goal: remission
    • Cytarabine + daunorubicin or idarubicin
    • Additional targeted agent depending on the specific mutation (e.g., midostaurin for AML with FLT3 mutation)
    • Associated with multiple adverse effects, which may require prolonged hospitalization: 
      • Bleeding
      • Infection
      • Cytopenias
      • Tumor-lysis syndromes
      • Electrolyte abnormalities
    • Frail patients may be given lower-intensity treatment.
  • Consolidation:
    • Goal: reduce risk of relapse
    • Additional courses of chemotherapy (high-dose cytarabine)
    • Hematopoietic cell transplant (HCT) for high-risk disease or poor prognosis
  • Maintenance:
    • Goal: maintain remission
    • Low-dose chemotherapy (non-myelosuppressive) and/or a targeted agent
  • Different treatment for acute promyelocytic leukemia (APL) (formerly known as M3):
    • APL is the most malignant form of AML (a medical emergency):
      • Without treatment, median survival is < 1 month.
      • Presents with bleeding (DIC), and low WBCs and blasts
      • Distinguished by responsiveness to treatment with all-trans retinoic acid
      • Chromosomal translocation t(15;17) leads to a fusion protein, which functions as a receptor (retinoic acid receptor alpha (RARα))
    • Induction therapy includes all-trans retinoic acid + arsenic trioxide 
  • Allogeneic HCT: preferred for patients with a poor prognosis, especially < 60 years of age

Supportive therapy and monitoring

  • Monitor bone-marrow response.
  • Monitor for chemotherapy side effects (e.g., vomiting) and treat accordingly.
  • Red-cell and platelet transfusions for anemia and thrombocytopenia
  • Granulocyte colony-stimulating factor (G-CSF) for neutropenia
  • Dietary modification (neutropenic diet)
  • American Society of Clinical Oncology recommends:
    • Prophylactic antibacterial and antifungal therapy 
    • Prophylactic antiviral therapy (for Hepatitis B core antibody and HSV)
  • Surveillance monitoring for:
    • Relapse: AML recurs after complete remission
    • Refractory AML: no full response with remission induction therapy


  • AML survival rate in children: approximately 65%–70% (lower than ALL)
  • AML survival rate in adults (5-year survival decreases as age increases):
    • 25–39 years old: 49%
    • 40–59 years old: 33%
    • 60–69 years old: 13%
    • 70–79 years old: 3%
    • > 80 years old: 0%
  • Better prognosis:
    • < 50 years old
    • Good functional capacity/performance status (Karnofsky score > 60%)
    • Multidrug resistance (MDR1)-negative phenotype
    • No prior hematologic disorder, radiation therapy, or chemotherapy
    • t(8;21), inv(16)/t(16;16), t(15;17)
    • NPM1 mutation, CEBPA mutation
  • Worse prognosis:
    • Age > 60 years old
    • Poor functional capacity/performance status (Karnofsky score < 60%)
    • MDR1-positive phenotype
    • Prior hematologic disorder or therapy-related AML
    • Complex karyotypic abnormalities (e.g., 3q26 aberrations, t(6;9), -5, -7) 
    • Certain mutations: FLT3 internal tandem duplication, IDH1, IDH2

Acute lymphoblastic leukemia versus acute myeloid leukemia

Table: ALL versus AML
  • Vincristine, corticosteroids, asparaginase
  • ± Anthracycline (doxorubicin or daunorubicin)
  • Cytarabine + daunorubicin or idarubicin
  • Additional targeted agent (based on mutation)
  • Cytarabine
  • Methotrexate
  • Anthracyclines
  • Alkylating agents
  • Epipodophyllotoxins
Additional chemotherapy (cytarabine)
  • Oral 6-MP daily
  • Methotrexate weekly
  • Periodic vincristine, prednisone, and intrathecal therapy
Non-myelosuppressive chemotherapy and/or a targeted agent
Additional treatment
  • TKI (e.g., imatinib) given for t(9;22) translocation (Philadelphia chromosome)
  • CNS preventive therapy
Acute promyelocytic leukemia:
  • Medical emergency!
  • Give ATRA + arsenic trioxide.
Hematopoietic cell transplantationFor those with a poor prognosis
  • Better prognosis if < 50 years old
  • Prognosis affected by associated mutations

Differential Diagnosis

  • Acute lymphoblastic leukemia: hematologic neoplasms characterized by uncontrolled proliferation of lymphocytic precursors. Acute lymphoblastic leukemia is the most common childhood cancer. Normal marrow is replaced by malignant cells, followed by the circulation of immature WBCs. The clinical presentation consists of fatigue, bleeding, fever, and infection (related to anemia, thrombocytopenia, and lack of functional WBCs), occurring in days to weeks. Mass effects of malignant infiltration (in bone, liver, spleen) are common. Diagnosis is by peripheral blood smear and bone-marrow biopsy showing lymphoblasts. In contrast, AML is the proliferation of myeloblasts. Treatment is mainly chemotherapy. Acute lymphoblastic leukemia generally carries a better prognosis than AML.
  • Myelodysplastic syndrome (MDS): a group of clonal neoplasms with maturation defects, characterized by dysplasia, cytopenias, and immature bone-marrow precursors. Patients present near 70 years of age with symptoms of anemia, neutropenia, or thrombocytopenia. The bone-marrow evaluation shows cytopenia, dysplasia in 1 or more lineage, and blast cells in < 20% of marrow cellularity, which helps distinguish MDS. The increased cumulative risk of transformation to AML varies depending on the MDS subtype. Acute myeloid leukemia developing from MDS carries a poor prognosis.
  • Primary myelofibrosis: a neoplasm characterized by chronic myeloproliferation with nonclonal deposition of fibroblasts, resulting in bone-marrow fibrosis. The condition is associated with a genetic mutation (typically JAK2 mutation). Clinical findings include severe fatigue, weight loss, and hepatosplenomegaly. Laboratory studies include cytopenia and bone-marrow studies with a dry tap (representing extensive fibrosis), and may be like AML. Primary myelofibrosis can transform to AML, which is often the cause of death.
  • Leukemoid reaction: a WBC count > 50,000/μL from causes other than leukemia. Neutrophilia and prominent left shift, usually in response to infection, are typical. Findings include toxic granulation in the neutrophils and (most importantly) the presence of an obvious cause for the neutrophilia. Cytogenetic or molecular testing also distinguishes AML. Management is supportive with treatment of the underlying etiology and leukapheresis if hyperviscosity is present.


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