Immunophenotypic and enzymatic studies do not support the concept of mixed monocytic‐granulocytic differentiation in acute promyelocytic leukaemia (M3): a study of 44 cases

Abstract

Leukaemic promyelocytes from 30 cases of hypergranular and 14 cases of hypogranular acute promyelocytic leukaemia (M3) were analysed for the presence of monocyte-associated characteristics to determine whether there was any evidence of mixed (hybrid) granulocytic-monocytic differentiation. Cytochemically, a high proportion of hypergranular cases showed significant alpha-naphthyl acetate esterase (ANAE) staining and simultaneous chloroacetate esterase, and ANAE expression by single cells was commonly seen. These atypical staining patterns were, however, not a feature of hypogranular cases. Immunophenotypic studies revealed that most hypergranular M3 cases were HLA-DR- and that monocyte-associated membrane CD14 expression was low in all cases tested. In addition, serum lysozyme concentrations (20 cases) were generally within the normal range and thus inconsistent with monocytic involvement in the leukaemic process. The significance of atypical ANAE staining of leukaemic promyelocytes was further examined by analysing ANAE isoenzyme components (defined by isoelectric focusing) in 11 cases. The patterns obtained (G1 and G2) were identical to those found in normal granulocytes and did not show any evidence of monocyte-associated esterase isoenzyme expression. On the basis of these findings, it is considered that the differentiation process in acute promyelocytic leukaemia is relatively well conserved and that the atypical esterase cytochemistry of hypergranular promyelocytes does not reflect their mixed lineage nature but is simply a consequence of increased granulation.

Microgranular and t(11;17)/PLZF‐RARα variants of acute promyelocytic leukemia also present the flow cytometric pattern of CD13, CD34, and CD15 expression characteristic of PML‐RARα gene rearrangement

“…Five studies showed no difference in the antigenic expression of the tested markers between classical and microgranular APL [14,[27][28][29][30]. A positive correlation of the expression of CD34 and/or of CD2 with the microgranular variant was described in five studies.…”

“…Among ten studies selected to compare our data [14,25,[27][28][29][30][31][32][33][34], no one had used so many different markers as we did. Five studies showed no difference in the antigenic expression of the tested markers between classical and microgranular APL [14,[27][28][29][30]. A positive correlation of the expression of CD34 and/or of CD2 with the microgranular variant was described in five studies.…”

HLA-DR antigen-negative acute myeloid leukemia

“…[8][9][10][11][12][13] HLA Class II molecules are expressed on acute myeloid leukemia (AML) blasts at diagnosis in most cases of AML, with the exception of acute promyelocytic leukemia (APL), which is characterized by lack of HLA-DR antigen expression. [14][15][16][17] Absence of HLA-DR antigen expression is rare in non-APL cases, 18 and little information is available about the clinical significance of lack of expression of these antigens.…”