In vitro functional defects of bone marrow-derived CD34+ progenitors from newly diagnosed mature B-cell malignancies with bone marrow tumor involvement.

Abstract : OBJECTIVE: We hypothesized that the presence of tumor cells in bone marrow (BM) could alter hematopoietic progenitor cell functions. Therefore, we evaluated phenotypic and in vitro functional properties of BM-derived CD34+ progenitors issued from untreated and newly diagnosed patients presenting a mature B-lymphoproliferative disorder (LPD) involving the BM (Inv+). PATIENTS AND METHODS: In vitro proliferation and differentiation capacities of primitive and committed progenitors were evaluated by cobblestone area-forming cell (CAFC) and colony-forming cell (CFC) assays, and ex vivo cell expansion. Migratory capacities of CD34+ cells were explored by chemotaxis assays using a CXCL12alpha gradient. RESULTS: Our results showed that CD34+ cells from Inv+ patients overexpressed CD117 and had a significant decrease of week-3 and -6 CAFC, and CFC frequencies, compared to cells obtained from healthy volunteers and LPD patients without BM involvement (Inv-). In addition, progenitors from Inv+ patients maintained a significantly decreased CFC capacity after ex vivo cell expansion, compared to healthy volunteers. However, the former cells held their migratory capacity in response to CXCL12alpha. CONCLUSION: Functional defects of primitive and committed CD34+ progenitors detected among LPD patients with BM tumor involvement suggest either that tumor cells may induced bystander effects on progenitors or that "unusual" CD34+ cells may exist in the BM that could belong to the proliferating tumor tissue.
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https://hal.archives-ouvertes.fr/hal-00453118
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Submitted on : Wednesday, February 3, 2010 - 9:12:19 PM
Last modification on : Wednesday, September 5, 2018 - 5:04:02 PM

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Patricia Amé-Thomas, Frédéric Deschaseaux, Frédéric Mauny, Claude-Eric Bulabois, Thierry Lamy, et al.. In vitro functional defects of bone marrow-derived CD34+ progenitors from newly diagnosed mature B-cell malignancies with bone marrow tumor involvement.. Experimental Hematology, Elsevier, 2005, 33 (3), pp.318-28. ⟨10.1016/j.exphem.2004.11.016⟩. ⟨hal-00453118⟩

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