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

被引：69

作者：

Ding, Wei ^{[1
]}

Nowakowski, Grzegorz S. ^{[1
]}

Knox, Traci R. ^{[1
]}

Boysen, Justin C. ^{[1
]}

Maas, Mary L. ^{[2
]}

Schwager, Susan M. ^{[1
]}

Wu, Wenting ^{[3
]}

Wellik, Linda E. ^{[1
]}

Dietz, Allan B. ^{[2
]}

Ghosh, Asish K. ^{[1
]}

Secreto, Charla R. ^{[1
]}

Medina, Kay L. ^{[4
]}

Shanafelt, Tait D. ^{[1
]}

Zent, Clive S. ^{[1
]}

Call, Timothy G. ^{[1
]}

Kay, Neil E. ^{[1
]}

机构：

[1] Mayo Clin, Div Hematol Oncol, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

[3] Mayo Clin, Canc Ctr Stat, Rochester, MN 55905 USA

[4] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2009年 / 147卷 / 04期

关键词：

B-cells; cell signalling; chronic lymphocytic leukaemia; mesenchymal cells; stromal cell; CHRONIC LYMPHOCYTIC-LEUKEMIA; CD38; EXPRESSION; STROMAL CELLS; ALPHA-4-BETA-1; INTEGRIN; PROLIFERATION CENTERS; PERIPHERAL-BLOOD; LYMPH-NODES; MARROW; APOPTOSIS; SURVIVAL;

D O I：

10.1111/j.1365-2141.2009.07868.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：471 / 483

页数：13

共 47 条

[1] T-cell suppression mediated by mesenchymal stem cells is deficient in patients with severe aplastic anemia [J].