Concept of Acute Myeloid Leukemia (AML) FAB Classification

There is no need of mnemonics to remember the FAB classification of Acute Myeloid Leukemia (AML); just remember the process myeloid differentiation. A simple schematic diagram with few intermediate processes and stimulating factors eliminated will meet our purpose here.

The cells belonging to the myeloid lineage are:

1. Granulocytes: Neutrophils, Eosinophils and Basophils
2. Monocytes and Macrophages
3. Erythrocytes (RBCs)
4. Megakaryocytes (Platelets)

In French-American-British (FAB) classification of AML, it is classified from M0 to M7. The scheme takes into account:

• The degree of maturation (M0 to M3)
• The lineage of leukemic blast (M4 to M7)

1. M0 – undifferentiated progenitor cells
2. M1 to M3 – myelocytes (granulocyte precursors)
3. M4 to M5 – monocyte precursors
4. M6 – erythrocyte precursors
5. M7 – platelet precursors

Simplified FAB classification of AML

1. M0 – Undifferentiated
2. M1 – Myeloblastic without maturation
3. M2 – Myeloblastic with maturation (Commonest type)
4. M3 – Promyelocytic
5. M4 – Myelomonocytic (Naegeli type)
6. M5 – Monocytic (Schilling type)
7. M6 – Erythroleukemia (Di Gulielmo’s disease)
8. M7 – Megakaryocytic

AML Concepts in Concise

1. FAB used 30% blasts to delineate chronic myeloid leukemia (CML) from Blast crisis and AML. WHO revised classification uses the presence of ≥20% myeloblasts in the bone marrow or peripheral blood for the diagnosis of AML.

2. Mo, M1 and M2:

• <3% blasts are MPO positive in M0 and ≥3% blasts are MPO positive in M1
• <10% maturation beyond myeloblasts = M1
• >10% mauration beyond myeloblasts = M2
• Auer rods:
  • M0 – None
  • M1 – 50%
  • M2 – 70%
  • M3 – 100%
• t(8:21) is pressent in M2

3. M3:

• Most cases have t(15:17) – results in disruption of Retinoic Acid Receptor (RAR) required for myeloblast maturation.
• All-trans-retinoic acid is hence, used for treatment of Acute Promyelocytic Leukemia (APL).
• DIC is seen in 5-10% cases due to prothrombotic release of Auer rods.

4. M4: >20% monocytic precursors (<20% in M2)

• Myeloperoxidase positive (Myeloblastic) + Auer rod positive (Monoblastic) + Non-specific esterase positive (Monoblastic)

5. M5:

• >80% monocytic precursors
• Gum infiltration and hyperplasia
• High lysozyme level
• Auer rod negative + Non-specific esterase positive

6. M6:

• ≥50% erythroid precursors and ≥20% blasts in nonerythroid component
• Also known as Di Gulielmo’s disease or Syndrome

7. M7:

• Rapid myelofibrosis due to release of PDGF.
• Resistant to treatment
• GATA1 mutations is seen in those associated with Down’s Syndrome.
• GpIIb/IIIa or vWF positive

8. Ara-C (Cytarabine) is used for the treatment of CML except M3, in which all-trans retinoic acid is used.

9. Remission criteria:

• Complete remission = Bone marrow blasts <5%, No auer rods
• Complete blood count recovery = ANC >1000/microlitre and Platelets ≥1,00,000/microlitre
• Partial remission = ≥50% fall in blasts over pretreatment values

10. M8:

• There is no M8 in FAB classification, but some authors have proposed rare deno-vo Acute Basophilic Leukemia as M8.