Although no specific chromosomal abnormalities have been found in AML, minimally differentiated point mutations of the AML1 gene have been observed in approximately 25% of cases. This mutation appears to correlate clinically with a higher white blood cell count and greater marrow blast involvement.[57,59] Mutation of FLT3, a receptor tyrosine kinase gene, occurs in approximately 25% of cases and has been associated with short survival.[40,59] The median OS is approximately 10 months.
Acute myeloblastic leukemia without maturation (FAB Classification M1)
AML without maturation is characterized by a high percentage of bone marrow blasts with little evidence of maturation to mature neutrophils and comprises approximately 10% of cases of AML. Most patients are adults. Patients usually present with anemia, thrombocytopenia, and neutropenia. (For information on anemia, refer to the PDQ summary on Fatigue.)
Common morphologic and cytochemical features include the following:
- Myeloblasts of 90% or more of the nonerythroid cells in the bone marrow.
- Myeloblasts that may have azurophilic granules and/or Auer rods.
- Myeloblasts that resemble lymphoblasts.
- MPO and SBB positivity in blasts of 3% or more.
- Typically markedly hypercellular marrow.
Immunophenotyping reveals blasts that express at least two myelomonocytic antigens (CD13, CD33, CD117) and/or MPO. CD34 is often positive. The differential diagnosis includes ALL in cases of AML without maturation with no granules and a low percentage of MPO positive blasts, and AML with maturation in cases of AML with maturation with a high percentage of blasts.
Although no specific chromosomal abnormality has been identified for AML without maturation, mutation of the FLT3 gene has been associated with leukocytosis, a high percentage of bone marrow blast cells, and a worse prognosis.[40,57,61]
Acute myeloblastic leukemia with maturation (FAB Classification M2)
AML with maturation is characterized by 20% or more myeloblasts in the blood or bone marrow and 10% or more neutrophils at different stages of maturation. Monocytes constitute less than 20% of bone marrow cells. This AML comprises approximately 30% to 45% of cases of AML. While it occurs in all age groups, 20% of patients are less than 25 years and 40% of patients are 60 years or older. Patients frequently present with anemia, thrombocytopenia, and neutropenia. (For information on anemia, refer to the PDQ summary on Fatigue.)
Morphologic features include the following:
- Myeloblasts with and without azurophilic granules.
- Auer rods.
- Promyelocytes, myelocytes, and neutrophils 10% or more of the bone marrow cells.
- Abnormal nuclear segmentation in neutrophils.
- Increased eosinophil precursors (frequently).
- Hypercellular marrow (usually).
- Blasts and maturing neutrophils reactive with antibodies to MPO and lysozyme.
With immunophenotyping, the blasts typically express one or more myeloid-associated antigens (CD13, CD33, and CD15). The differential diagnosis includes: RAEB in cases with a low blast percentage, AML without maturation when the blast percentage is high, and AMML in cases with increased monocytes.