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

Wei Ding, Grzegorz S. Nowakowski, Traci R. Knox, Justin C. Boysen, Mary L. Maas, Susan M. Schwager, Wenting Wu, Linda E. Wellik, Allan B. Dietz, Asish K. Ghosh, Charla R. Secreto, Kay L. Medina, Tait D. Shanafelt, Clive S. Zent, Timothy G. Call, Neil E. Kay

Research output: Contribution to journalArticle

53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)471-483
Number of pages13
JournalBritish journal of haematology
Volume147
Issue number4
DOIs
StatePublished - Nov 2009

Keywords

  • B-cells
  • Cell signalling
  • Chronic lymphocytic leukaemia
  • Mesenchymal cells
  • Stromal cell

ASJC Scopus subject areas

  • Hematology

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    Ding, W., Nowakowski, G. S., Knox, T. R., Boysen, J. C., Maas, M. L., Schwager, S. M., Wu, W., Wellik, L. E., Dietz, A. B., Ghosh, A. K., Secreto, C. R., Medina, K. L., Shanafelt, T. D., Zent, C. S., Call, T. G., & Kay, N. E. (2009). Bi-directional activation between mesenchymal stem cells and CLL B-cells: Implication for CLL disease progression. British journal of haematology, 147(4), 471-483. https://doi.org/10.1111/j.1365-2141.2009.07868.x