AML (Acute Myelogenous Leukemia with maturation) (M2)

Definition

Acute Myeloblastic Leukemia with maturation- FAB M2:   AML-M2 is defined and characterized by the presence of > 20% blasts in the bone marrow or blood and evidence of maturation to more mature neutrophils. (>10% neutrophils are at different stages of maturation). Monocytes comprise <20% of bone marrow cells. 

Sample Cases

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Epidemiology

AML-M2 comprises approximately 30-45% of cases of AML. It occurs in all age groups; 20% of patients are less than 25 years of age and 40% are >60 years of age.

Possible causes

Unknown

Morphology

In some cases the immature cells have abundant, frequently basophilic cytoplasm, with variable numbers of often indistinct, sometimes coalescent granules. If such immature cells are < 10% the diagnosis is M1, but if > 10% the diagnosis becomes AML-M2.   AML-M2 shows significant maturation: Type II blasts are common and Auer rods are frequent (promyelocytes-myelocytes).

Typical morphology of AML-M2. note presence of myeloid maturation.

Immunophenotyping

The CD45 vs SSC gating dot plot shows a population with medium to high SSC and moderate CD45. This is due to the presence of varying maturation stages of neutrophils.

AML-M2 cases contain both myeloblasts and myeloid precursors, as in this case.

 Below are selected dot plots from an AML-M2 case.           

CD33 and MPO are positive on the blasts. Mo2 is negative and CD11b is partially expressed.	CD56, CD13 and HLA Dr are positive on the blasts.	CD15 and MPO are positive on the blasts, though CD34 and CD117 are not expressed.

The gated blasts in AML-M2 must express one or more of the myeloid associated antigens, CD13(mod), CD33(bright), and CD15. They may express CD117, CD34 and HLA Dr. CD4 may be present, but dim. These blasts may also express CD7 and/or CD56. These blasts are generally negative for the monocytic markers CD14 and CD11b.                                   

Other relevant tests

Cytochemistry: The blasts are largely MPO positive. NSE and PAS are generally negative.

Genetics: Cases with increase basophils may have recurrent abnormalities including translocations and deletions at 12p (11-13) and t(6;9)(p23;q34).  AML with the t(8;21)(q22;q22) is usually an AML-M2 and has a more favorable prognosis.   

Flow Diagnosis

AML-M1 and AML-M2 are initially stratified by morphology (see above). M2 blasts  must express at least two of the following myeloid antigens:  CD13,  CD33, CD15, CD117, MPO and/or HLA-DR. MPO must be > 3% on blasts.

References

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