Title:Functional and Clinical Significance of the Integrin Alpha Chain CD49d Expression in Chronic Lymphocytic Leukemia
Volume: 16
Issue: 8
Author(s): Michele Dal Bo, Erika Tissino, Dania Benedetti, Chiara Caldana, Riccardo Bomben, Giovanni Del Poeta, Gianluca Gaidano, Francesca Maria Rossi, Pietro Bulian, Antonella Zucchetto and Valter Gattei
Affiliation:
Keywords:
CD49d, CLL, integrin, microenvironment, prognosis, therapy.
Abstract: Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease
characterized by the accumulation/expansion of a clonal population of neoplastic
cells with the morphological appearance of small mature B lymphocytes in
blood, bone marrow, and lymphoid organs. CD49d, the α chain of the α4β1 integrin
heterodimer, is one of the main interactors between CLL cells and accessory
cells in the microenvironmental sites and one of the main predictors of overall
survival. In particular, CD49d is known to play a pivotal role in mediating both
cell-cell and cell-matrix interactions in CLL-involved tissues eventually delivering
prosurvival signals and protecting CLL cells from drug-induced damages.
Treatment strategies targeting the α4β1 integrin could represent an interesting option
in CLL. In this context, the recombinant anti-CD49d antibody natalizumab demonstrated the potential
to overcome stromal cell-induced resistance of B cell lymphoma cells against cytotoxic drugs
and rituximab in vitro. Moreover, a specific interest for the CD49d molecule raises from the clinical
activity of the recently proposed inhibitors of kinases downstream the BCR that has been recently related
with the inside-out activation of the α4β1 integrin. In the review, we addressed in detail the role
of CD49d in CLL cells, including clinical impact, relationship with specific cytogenetic features, and
CD49d-dependent interactions in lymph node and bone marrow microenvironment responsible for
growth- and survival- supporting signals, eventually influencing CLL prognosis and therapeutic options.