Poorly or Minimally Differentiated Acute Myeloid Leukemia

According to the National Cancer Institute workshop on AML definition310 and the FAB criteria on AML-M0,10 FAB-M0, the AML subtype with the least morphologic differentiation, is diagnosed on the basis of ultrastructural evidence of MPO and/or blast cell reactivity with at least one "lineage-specific" myeloid antigen (e.g., CD33, CD13) in the absence of the lym-phoid markers. Immunophenotypic profiles found in the literature to describe minimally differentiated AML reflect antigen expression patterns established in morphologically defined FAB-M0 leukemia.147'191'365-367 As a result, minimally differentiated AML, as an immunophenotypic subgroup, represents a heterogeneous accumulation of immature leukemias. Unfortunately, a proposal by Stasi and Amadori146 of new diagnostic criteria for this AML type does not include a change in this basically misleading approach.

We have taken the opposite approach by establishing the morphology of patients with immunophenotypically defined minimally differentiated AML, defined by low expression of CD65s (30 percent or less of blast cells).15 The FAB subtypes within this immunologically homogeneous group differed markedly, with a high percentage of FAB-M0 and M1 accounting, however, for only about 60 percent of cases. It is a misconception that MPO invariably detects the earliest stages of AML.368 In agreement with Storr et al.,292 we have found MPO expression in significantly fewer blast cells from patients with minimally differentiated than from those with differentiated AML and have, in fact, seen examples of unequivocally myeloid leukemias lacking MPO and expressing solely CD33 and/or CD13.15 In AML, intracytoplas-

mic369,370 or membrane CD1315 appears to represent one of the earliest or the earliest sign of myeloid differentiation. Minimally differentiated myeloblasts correspond to the level of early CFU-GM and accordingly lack more mature myeloid antigens (CD65(s), CD15(s)) but frequently express stem cell features. If CD11b is present, the diagnosis of CD11b+ AML must be considered.25 In MPOlow/- minimally differentiated AML, it is important to exclude megakaryocytic or erythroid leukemias.

Low and/or absent CD34 and/or HLA-DR and/or CD13 antigen despite CD33 expression should be explored further to exclude immature acute basophilic or mast-cell leukemia. The blasts may express variable MPO activity, and basophilic or mast-cell granulation by light microscopy is commonly absent.371

Given that data reported are derived from heterogeneous groups of leukemias, including obvious cases of ALL,372 the prognosis of minimally differentiated AML is difficult to evaluate from the literature. The unfavorable outcome observed in some studies may be related to older age,15 frequent expression of Pgp,373 a high incidence of unfavorable cytogenetics, such as complex abnormalities and chromosome 5 or 7 aberra-tions,374,375 or simply the high degree of immunologically defined blast cell immaturity.303

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