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


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.


CONCLUSIONS
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.
Amé-Thomas
Patricia
P
Department of Hematology, University Hospital Jean Minjoz, Besançon, France.
Deschaseaux
Frédéric
F
Mauny
Frédéric
F
Bulabois
Claude-Eric
CE
Lamy
Thierry
T
Hervé
Patrick
P
Cahn
Jean-Yves
JY
Fest
Thierry
T
D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D001402:B-Lymphocytes; D001853:Bone Marrow / Q000503:physiopathology*; D019046:Bone Marrow Neoplasms / Q000503:physiopathology* / Q000556:secondary; D024201:Bystander Effect; D016022:Case-Control Studies; D005260:Female; D006412:Hematopoietic Stem Cells; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged
D018952:Antigens, CD34