Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression.
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.
Ding
Wei
W
Division of Hematology/Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Nowakowski
Grzegorz S
GS
Knox
Traci R
TR
Boysen
Justin C
JC
Maas
Mary L
ML
Schwager
Susan M
SM
Wu
Wenting
W
Wellik
Linda E
LE
Dietz
Allan B
AB
Ghosh
Asish K
AK
Secreto
Charla R
CR
Medina
Kay L
KL
Shanafelt
Tait D
TD
Zent
Clive S
CS
Call
Timothy G
TG
Kay
Neil E
NE
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D018450:Disease Progression; D004789:Enzyme Activation / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D008875:Middle Aged; D009367:Neoplasm Staging; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011990:Receptors, Transferrin / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; C068126:CD71 antigen; D011990:Receptors, Transferrin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases