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The CD49d/CD29 complex is physically and functionally associated with CD38 in B-cell chronic lymphocytic leukemia
A Zucchetto1, T Vaisitti, D Benedetti
1Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.
Leukemia
|February 1, 2012
Summary
The co-expression of CD49d and CD38 in chronic lymphocytic leukemia (CLL) enhances cell adhesion and survival. This interaction explains the poor prognosis associated with these markers in aggressive CLL.
Area of Science:
- Immunology
- Hematology
- Molecular Biology
Background:
- CD49d and CD38 are established negative prognostic indicators in chronic lymphocytic leukemia (CLL).
- Co-expression of CD49d and CD38 identifies a CLL subset with a particularly aggressive clinical course.
Purpose of the Study:
- To investigate the physical association between the CD49d/CD29 integrin complex and CD38 in CLL cells.
- To elucidate the functional role of CD38 in CD49d-mediated cell adhesion and its impact on CLL cell behavior and survival.
Main Methods:
- Demonstrated physical association using cocapping, coimmunoprecipitation, and cell adhesion assays.
- Utilized primary CLL cells and B-cell lines, including CD38 transfectants of the Mec-1 cell line.
- Assessed cell adhesion to CD49d-specific substrates, changes in cell morphology, Vav-1 phosphorylation, F-actin distribution, and apoptosis resistance.
Main Results:
- Confirmed a constitutive physical association between CD49d/CD29 and CD38 in CLL cells.
- CD49d(+)CD38(+) CLL cells exhibited significantly enhanced adhesion to CD49d substrates compared to CD49d(+)CD38(-) cells.
- Adherent CD49d(+)CD38(+) cells showed altered morphology, increased Vav-1 phosphorylation, and greater resistance to apoptosis.
Conclusions:
- CD38 plays a direct role in augmenting CD49d-mediated cell adhesion in CLL.
- The enhanced adhesion and survival conferred by CD38 in co-expressing CLL cells contribute to their aggressive clinical behavior and poor prognosis.
