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

Minimally differentiated acute myeloid leukemia (AML-M0) is a rare FAB subt ype (2-3% of AMLs) of poor prognosis. The aim of our study was to character ize AML-MO expression and regulation of adhesion/costimulatory molecule inv olved 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-NIO in primary mixed lymphocyte reactio n, as evaluated by IL-2 secretion of responding T cells, is reduced in comp arison with more differentiated subtypes (128 +/- 95 pg/ml vs 304 +/- 159 p g/ml, P < 0.05). These data are in line with low blast cell expression of m ajor histocompatibility complex (MHC) class II DR molecules, and of the CD2 8 ligand B7-2, which plays an important role in AML immune recognition. Adh esion/costimulatory molecules were up-regulated by leukemic cell stimulatio n via CD40, and, although less efficiently, by gamma-IFN; both stimuli impr oved blast cell immunogenicity. We also demonstrate that AML-M0 have a very high percentage (40% +/- 30) of CD34(+)/CD38(-) leukemic clonogenic precur sors in comparison with more differentiated AMLs (2.5% +/- 2) or non-leukem ic CD34(+) hematopoietic precursors (1.8% +/- 0.8). Since the presence of a leukemic cell population at an early differentiation stage has been identi fied as a poor prognostic factor, we conclude that the high frequency of CD 34(+)/CD38(-) blasts in AML-M0 may converge with already identified poor pr ognosis factors such as chemotherapy resistance and cytogenetic abnormaliti es. The clinical implications of AML-M0 impaired in vitro immunogenicity an d a high percentage of CD34(+)/CD38(-) blasts will require comparative anal ysis of additional patients. The increased immunogenicity of blast cells af ter CD40 triggering provide interesting clues for AML-M0 immunotherapy, tha t have to be confirmed with an in vivo leukemia model in mice.