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

Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression.
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DOI:
10.1111/j.1365-2141.2009.07868.x
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发表时间:
2009-11
影响因子:
6.5
通讯作者:
Kay NE
Kay NE
中科院分区:
医学2区
文献类型:
--
作者:
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

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It was hypothesized that contact between chronic lymphocytic leukemia (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. Up-regulation of CD71, CD25, CD69 and CD70 in CLL B-cells was found in the co-culture. CD71 up-regulation 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.
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