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 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 gamma-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.
Costello
R
R
Immunologie des Tumeurs, Département d'Hématologie, Institut Paoli-Calmettes, Université de Méditerranée, Marseille, France.
Mallet
F
F
Chambost
H
H
Sainty
D
D
Arnoulet
C
C
Gastaut
J A
JA
Olive
D
D
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000208:Acute Disease; D000818:Animals; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000097:blood*; D000943:Antigens, Differentiation / Q000097:blood*; D000970:Antineoplastic Agents / Q000494:pharmacology; D019013:CD40 Antigens / Q000097:blood; D015815:Cell Adhesion Molecules / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins; D051379:Mice; D009244:NAD+ Nucleosidase / Q000097:blood*; D014411:Neoplastic Stem Cells / Q000276:immunology*
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1