期刊
CURRENT CANCER DRUG TARGETS
卷 16, 期 8, 页码 659-668出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1568009616666160809102219
关键词
CD49d; CLL; integrin; microenvironment; prognosis; therapy
类别
资金
- Associazione Italiana Ricerca Cancro (AIRC) [IG-13227, MFAG-10327]
- Progetto Ricerca Finalizzata I.R.C.C.S [RF-2009-1469205, RF-2010-2307262]
- Progetto Giovani Ricercatori [GR-2009-1475467]
- Ministero della Salute, Rome, Italy
- Fondazione Internazionale di Ricerca in Medicina Sperimentale (FIRMS) Turin, Italy
- Associazione Italiana contro le Leucemie, linfomi e mielomi (AIL), Venezia Section, Pramaggiore Group, Italy
- Ricerca Scientifica Applicata, Regione Friuli Venezia Giulia (Linfonet Project), Trieste, Italy
- 5x1000 Intramural Program, Centro di Riferimento Oncologico, Aviano, Italy
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 a chain of the alpha(4)beta(1) 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 a4 beta 1 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 alpha 4 beta 1 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.
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