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

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-ly...

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Bibliographic Details
Published in:Experimental hematology 2005-03, Vol.33 (3), p.318-328
Main Authors: Amé-Thomas, Patricia, Deschaseaux, Frédéric, Mauny, Frédéric, Bulabois, Claude-Eric, Lamy, Thierry, Hervé, Patrick, Cahn, Jean-Yves, Fest, Thierry
Format: Article
Language:English
Subjects:
Adult
Aged
Antigens, CD34
B-Lymphocytes
Bone Marrow
Bone Marrow - physiopathology
Bone Marrow Neoplasms
Bone Marrow Neoplasms - physiopathology
Bone Marrow Neoplasms - secondary
Bystander Effect
Case-Control Studies
Female
Hematopoietic Stem Cells
Humans
Life Sciences
Lymphoproliferative Disorders
Lymphoproliferative Disorders - physiopathology
Male
Middle Aged
Santé publique et épidémiologie
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Summary: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 +). 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 CXCL12α gradient. 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 CXCL12α. 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
ISSN:0301-472X
1873-2399
DOI:10.1016/j.exphem.2004.11.016