The immunophenotype of minimally differentiated acute myeloid leukemia (AML-M0): reduced immunogenicity and high frequency of CD34+/CD38 leukemic progenitors

Abstract

Minimally differentiated acute myeloid leukemia (AML-M0) is a rare FAB subtype (2–3% of AMLs) of poor prognosis. The aim of our study was to characterize AML-M0 expression and regulation of adhesion/costimulatory molecule involved in immune recognition, to test blast in vitro immunogenicity, and to determine the percentage of leukemia progenitor cells. Here, we demonstrate that alloimmune recognition of AML-M0 in primary mixed lymphocyte reaction, as evaluated by IL-2 secretion of responding T cells, is reduced in comparison with more differentiated subtypes (128 ± 95 pg/ml vs304 ± 159 pg/ml, P < 0.05). these data are in line with low blast cell expression of major histocompatibility complex (mhc) class ii dr molecules, and of the cd28 ligand b7-2, which plays an important role in aml immune recognition. adhesion/costimulatory molecules were up-regulated by leukemic cell stimulation via cd40, and, although less efficiently, by γ-ifn; both stimuli improved blast cell immunogenicity. we also demonstrate that aml-m0 have a very high percentage (40% ± 30) of cd34+/CD38 leukemic clonogenic precursors in comparison with more differentiated AMLs (2.5% ± 2) or non-leukemic CD34+hematopoietic precursors (1.8% ± 0.8). Since the presence of a leukemic cell population at an early differentiation stage has been identified as a poor prognostic factor, we conclude that the high frequency of CD34+/CD38 blasts in AML-M0 may converge with already identified poor prognosis factors such as chemotherapy resistance and cytogenetic abnormalities. The clinical implications of AML-M0 impaired in vitroimmunogenicity and a high percentage of CD34+/CD38 blasts will require comparative analysis of additional patients. The increased immunogenicity of blast cells after CD40 triggering provide interesting clues for AML-M0 immunotherapy, that have to be confirmed with an in vivo leukemia model in mice.

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Correspondence to D Olive.

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Costello, R., Mallet, F., Chambost, H. et al. The immunophenotype of minimally differentiated acute myeloid leukemia (AML-M0): reduced immunogenicity and high frequency of CD34+/CD38 leukemic progenitors. Leukemia 13, 1513–1518 (1999). https://doi.org/10.1038/sj.leu.2401519

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Keywords

  • acute myeloid leukemia
  • AML-M0
  • leukemia progenitors
  • immune recognition
  • CD34
  • CD38

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