The role of CD44 in the pathophysiology of chronic lymphocytic leukemia
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Volume
6
Publisher
Publisher URL
DOI
10.3389/fimmu.2015.00177
Journal
FRONTIERS IN IMMUNOLOGY
ISSN
1664-3224
Metadata
Show full item recordAbstract
CD44 interactions with hyaluronan (HA) play a key role in various malignancies, supporting
tumor cell migration, adhesion, and survival. In contrast to solid tumors, the expression of
CD44 standard and variant forms and their functional interplay with HA is less understood
in hematological malignancies. Chronic lymphocytic leukemia (CLL) is a highly abundant Bcell malignancy with a well coordinated balance between cell cycle-arrest and proliferation
of tumor subpopulations.The long-term survival and proliferation of CLL cells requires their
dynamic interactions with stromal and immune cells in lymphoid organs. Interactions of HA
with CD44 and HA-mediated motility receptor (RHAMM) contribute to CLL cell localization,
and hence CLL pathophysiology, by shaping homing, interstitial migration, and adhesion of
the tumor cells. CD44 can complex with key prognostic factors of CLL, particularly CD38
and CD49d, bridging the gap between prognosis and cellular function. Here, we review the
current evidence for the individual and associated contributions of CD44 to CLL pathophysiology, the dynamic functional regulation of CD44 upon CLL cell activation, and possible
therapeutic strategies targeting CD44 in CLL.