The Role of CD49d in Chronic Lymphocytic Leukaemia: Microenvironmental Interactions and Clinical Relevance

*Michele Dal Bo,1 Erika Tissino,1 Dania Benedetti,1 Chiara Caldana,1 Riccardo Bomben,1 Giovanni Del Poeta,2 Gianluca Gaidano,3 Francesca Maria Rossi,1 Antonella Zucchetto,1 Valter Gattei1

1. Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy
2. Division of Hematology, S. Eugenio Hospital and University of Rome Tor Vergata, Rome, Italy
3. Division of Hematology, Department of Clinical and Experimental Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
*Correspondence to

Disclosure: No potential conflict of interest.
Received: 25.03.14 Accepted: 20.05.14
Citation: EMJ Hema. 2014;1:80-87.


Chronic lymphocytic leukaemia (CLL) is a clinically heterogeneous disease characterised 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. Stimulation through the B cell receptor (BCR) plays a prominent role in the selection and expansion of the malignant clone in CLL. On the other hand, other external signals delivered by several cell types including T lymphocytes, macrophages, stromal cells, endothelial cells, and follicular dendritic cells, operating through either direct BCR-independent cell-cell contact or indirect production of paracrine soluble factors, synergistically cooperate in regulating proliferation and survival of CLL cells. In this context, CD49d is known to play a pivotal role in mediating both cell-cell and cell-matrix interactions in CLL-involved tissues, eventually delivering pro-survival signals and protecting CLL cells from drug-induced damages. In the present review, we focused on functional and physical interactions of CD49d with other microenvironmental receptors, including CD38 and BCR, and other specific CD49d-dependent interactions in lymph node and bone marrow microenvironments responsible for growth and survival-supporting signals, eventually influencing CLL prognosis and therapeutic options.

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