The immunophenotype of minimally differentiated acute myeloid leukemia (AML-M0): reduced immunogenicity and high frequency of CD34+/CD38− leukemic progenitors
| Autor: | Danielle Sainty, C Arnoulet, Régis Costello, Jean-Albert Gastaut, Françoise Mallet, Hervé Chambost, Daniel Olive |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Antigens CD34 Antineoplastic Agents Biology CD38 Immunophenotyping Antigen-Antibody Reactions Interferon-gamma Mice NAD+ Nucleosidase Antigens CD hemic and lymphatic diseases Precursor cell medicine Animals Humans CD40 Antigens Progenitor cell ADP-ribosyl Cyclase Membrane Glycoproteins Immunogenicity Myeloid leukemia Cell Differentiation Hematology medicine.disease ADP-ribosyl Cyclase 1 Antigens Differentiation Haematopoiesis Leukemia Oncology Leukemia Myeloid Acute Disease Immunology Neoplastic Stem Cells Interleukin-2 Cell Adhesion Molecules |
| Zdroj: | Leukemia. 13:1513-1518 |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/sj.leu.2401519 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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