Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression.

Abstract:

:It was hypothesized that contact between chronic lymphocytic leukaemia (CLL) B-cells and marrow stromal cells impact both cell types. To test this hypothesis, we utilized a long-term primary culture system from bone biopsies that reliably generates a mesenchymal stem cell (MSC). Co-culture of MSC with CLL B-cells protected the latter from both spontaneous apoptosis and drug-induced apoptosis. The CD38 expression in previously CD38 positive CLL B-cells was up-regulated with MSC co-culture. Upregulation of CD71, CD25, CD69 and CD70 in CLL B-cells was found in the co-culture. CD71 upregulation was more significantly associated with high-risk CLL, implicating CD71 regulation in the microenvironment predicting disease progression. In MSC, rapid ERK and AKT phosphorylation (within 30 min) were detected when CLL B-cells and MSC were separated by transwell; indicating that activation of MSC was mediated by soluble factors. These findings support a bi-directional activation between bone marrow stromal cells and CLL B-cells.

journal_name

Br J Haematol

authors

Ding W,Nowakowski GS,Knox TR,Boysen JC,Maas ML,Schwager SM,Wu W,Wellik LE,Dietz AB,Ghosh AK,Secreto CR,Medina KL,Shanafelt TD,Zent CS,Call TG,Kay NE

doi

10.1111/j.1365-2141.2009.07868.x

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

471-83

issue

4

eissn

0007-1048

issn

1365-2141

pii

BJH7868

journal_volume

147

pub_type

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