Open AccessHypoxia Modifies Proliferation and Differentiation of CD34 + CML Cells
Author(s) -
Desplat Vanessa,
Faucher JeanLuc,
Mahon François Xavier,
Sbarba Persio Dello,
Praloran Vincent,
Ivanovic Zoran
Publication year - 2002
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.20-4-347
Subject(s) - biology , cd34 , haematopoiesis , progenitor cell , hypoxia (environmental) , tyrosine phosphorylation , stem cell , cell culture , microbiology and biotechnology , tyrosine kinase , cell growth , cell , immunology , phosphorylation , signal transduction , biochemistry , chemistry , oxygen , genetics , organic chemistry
We previously showed that hypoxia (1% O 2 ) favors the self‐renewal of murine and human normal hematopoietic stem cells. This study represents the first attempt to characterize the effects of hypoxia on the maintenance of chronic myeloid leukemia (CML) progenitors. CD34 + cells isolated from apheresis products of CML patients were incubated in hypoxia (1% O 2 ) and normoxia (20% O 2 ). After 8 days of culture, their proliferation, capacity for colony‐forming‐cell (CFC) generation in secondary cultures (pre‐CFC), and phenotype (CD34 and platelet‐activating factor receptor [PAF‐R]) were compared with those of normal cells, and tyrosine phosphorylation in CML cells was measured. Hypoxia inhibits the proliferation of CD34 + cells and preserves the pre‐CFC capacity and cell‐surface CD34 expression of CML cells better than normoxia. The PAF‐R expression, which was absent on freshly isolated cells, was detected at the cell surface in both populations after 8 days of culture, but with a lower percentage of positive cells in CML cell cultures. Incubation in hypoxia suppressed the PAF‐R expression of normal cells and increased it in CML cells, resulting in a similar expression in the two populations. These effects could be linked to inhibition by hypoxia of the tyrosine hyperphosphorylation of cellular proteins, a major hallmark of CML cells.