What is the characteristic cell type in Acute Myeloid Leukemia (AML) (Acute Myeloid Leukemia) subtype FAB (French-American-British classification) - M5a?

AML (FAB – M5a) is Characterized by the Presence of Monoblasts

AML FAB-M5a (acute monoblastic leukemia) is characterized by the predominance of monoblasts, which constitute at least 80% of the non-erythroid cells in the bone marrow.

Understanding AML FAB-M5a Classification

The French-American-British (FAB) classification system, while now largely replaced by the WHO classification, remains important for morphological characterization of AML subtypes. The M5 subtype is divided into two categories:

• M5a (acute monoblastic leukemia): Characterized by:

  • Predominance of monoblasts (≥80% of non-erythroid cells)
  • Monoblasts have delicate nuclear chromatin, prominent nucleoli, and abundant cytoplasm
  • Strong positivity for non-specific esterase staining

• M5b (acute monocytic leukemia): Characterized by:

  • Predominance of promonocytes and monocytes
  • Less than 80% monoblasts
  • More differentiated monocytic cells

Diagnostic Features of AML-M5a

Morphological Characteristics

• Large blast cells with abundant cytoplasm
• Round to oval nuclei with fine chromatin pattern
• Prominent nucleoli
• Minimal granulation
• Absence of Auer rods in most cases

Immunophenotypic Profile

• Expression of myeloid markers (CD13, CD33)
• Strong expression of monocytic markers:
  • CD14, CD4, CD11b, CD64, CD68
• CD68 and CD11b are expressed at higher levels in M5a compared to M5b 1

Cytogenetic and Molecular Features

• Heterogeneous karyotypes
• Common abnormalities include:
  • Rearrangements involving 11q23 (MLL gene)
  • t(8;16)(p11;p13) in some cases 2, 3

Clinical Significance and Prognosis

Despite historical concerns about poorer outcomes, modern data suggests that AML-M5a does not have a significantly worse prognosis than other AML subtypes. The Eastern Cooperative Oncology Group found that:

• Complete remission rates: 52% for M5a vs. 65% for M5b (not statistically significant)
• 3-year disease-free survival: 18% for M5a vs. 28% for M5b (not statistically significant)
• 3-year overall survival: 33% for M5a vs. 30% for M5b (not statistically significant) 4

Diagnostic Approach

According to current guidelines, diagnosis of AML requires:

1. Bone marrow aspirate and biopsy
2. Peripheral blood examination
3. Immunophenotyping by flow cytometry
4. Cytogenetic analysis
5. Molecular genetic testing 5

Treatment Considerations

Treatment follows standard AML protocols based on risk stratification determined by:

• Age
• Initial leukocyte count
• Cytogenetic profile
• Molecular genetic features 5

Risk stratification is crucial for determining appropriate therapy intensity and consideration for stem cell transplantation.

Key Pitfalls to Avoid

1. Misclassification: Don't confuse M5a (monoblastic) with M5b (monocytic) - the distinction is based on the percentage of monoblasts (≥80% in M5a)

2. Incomplete workup: Always perform comprehensive diagnostic evaluation including immunophenotyping, cytogenetics, and molecular studies

3. Overreliance on morphology alone: While monoblasts are characteristic of M5a, definitive diagnosis requires correlation with immunophenotyping and genetic studies

4. Prognostic assumptions: Don't assume worse outcomes based solely on M5a classification; prognosis depends more on genetic and molecular features than on FAB subtype

Remember that while the FAB classification provides important morphological information, the WHO classification incorporating genetic and molecular data is now the standard for risk stratification and treatment planning in AML.