University of Virginia Health System

Acute Myeloblastic Leukemia With Differentiation
(M2 AML)

(a) M2 AML- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(b) M2 AML with eosinophilia (M2Eo)-  Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(c) M2 AML with some acute basophilic leukemia features- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

Description:

This subtype is the most common one seen in adults, representing up to 30% of cases. 

The morphologic hallmark is evidence of maturation down the granulocytic line (a,b,c), much more than in the M1 AML subtype. Cells that have matured beyond the promyelocyte (e.g. myelocytes, metamyelocytes) are present. Most of the more differentiated cells are neutrophils but some are eosinophils, and rarely basophils. In many cases the maturing cells are dysplastic. The agranular blasts (type I blasts) cannot be distinguished from M0, M1 or L2 blasts by morphology alone on a Wright-Giemsa stained peripheral blood smear or bone marrow aspirate. The nuclear chromatin is somewhat coarser and may be clumped, and nucleoli usually are visible. Type II blasts often represent a significant portion of the total blasts. These blasts are similar to type I blasts except for the presence of a variable number of azurophilic granules in the cytoplasm. Unlike normal promyelocytes and early myelocytes, the Golgi apparatus is not seen or is poorly developed. Nuclear maturation lags behind the cytoplasmic maturation. Auer rods are frequently visible.

A variant of M2 AML associated with eosinophilia is recognized (M2Eo). The eosinophils may show mild atypia, particularly in the more immatures ones, characterized by the appearance of coarse cytoplasmic granules ranging in color from deeply basophilic, resembling primary or basophil granules to those that have a salmon-like color. The more mature eosinophils usually are not atypical.

Acute basophilic leukemia (M2Ba), a very rare subtype, is also an example of AML with differentation- in this case down the basophil lineage. The leukemic blasts are type II and the cytoplasmic granules are coarse and basophilic, resembling those in normal mature basophils, and the cytoplasm is basophilic in color and may contain vacuoles. Some of the more mature forms often are dysplastic (c). May occur de novo or as blast crisis in the chronic myeloproliferative disorders. 

Cytochemistry:

The blasts are positive for myeloperoxidase (MPO), Sudan black B, and chloroacetate esterase (reflecting the abortive maturation effort). The non-specific esterase stain is negative in the agranular blasts. In acute basophilic leukemia, the diagnostic finding is metachromatic positivity with toluidine blue.

Immunophenotype:  

• Stem cell and early hematopoietic progenitor cell markers: CD34+, HLA-DR+, Tdt±.
• Myeloid lineage markers: CD117+, CD13+, CD33+
• Lymphoid lineage markers: CD19, a B cell marker, is usually weakly positive, except in the acute basophilic subtype, and CD56±

Cytogenetics:

A signature cytogenetic abnormality, t(8;21) is seen in 30% or more of cases, and is seen more in the younger adults with this subtype. No signature cytogenetic abnormality has been identified in the acute basophilic subtype.

Clinical Features:

In addition to those discussed under acute leukemia in general, chloromas (granulocytic sarcomas) are seen more frequently. In acute basophilic leukemia, manifestations due to high circulating levels of histamine may occur. 

Prognosis:

Very good if the t(8;21) is present- more than 50% of these patients are probably cured with conventional chemotherapy alone. Prognosis unclear in acute basophilic leukemia due to the rarity of this subtype. In most reported cases, prognosis is poor.

General References:

• Bennett JM, Catovsky D, Daniel MT, et al: Proposed revised criteria for the classification of acute myeloid leukemia: A report of the French-American-British Cooperative Group. Am Intern Med 103:620, 1985
• Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. Pathology and genetics of tumors of hematopoietic and lymphoid tissues. Vol. 3 of World Health Organization classification of tumors, Lyon, France: IARC Press, 2001
• Nucufora G, Birn DJ, Erickson P, et al: Detection of DNA rearrangements in the AML1 and ETO loci and the AML1/ETO fusion mRNA in patients with t(8;21) acute myeloid leukemia. Blood 81:883, 1993
• Duchayne E, Demur C, Rubie H, et al: Diagnosis of acute basophilic leukemia. Leuk Lymphoma 32:269, 1999

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