Microenvironmental interactions in chronic lymphocytic leukemia: Hints for pathogenesis and identification of targets for rational therapy

Michele Dal Bo, Riccardo Bomben, Antonella Zucchetto, Giovanni Del Poeta, Gianluca Gaidano, Silvia Deaglio, Dimitar G. Efremov, Valter Gattei

Research output: Contribution to journalArticle

Abstract

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the accumulation/expansion of a clonal population of small mature B lymphocytes in blood, bone marrow, and lymphoid organs. Although initial genetic events are considered primarily responsible for the first step(s) of neoplastic transformation, the development and progression of the CLL clone are thought to be affected by various micro-environmental signals that regulate proliferation and survival of malignant B cells. In the present review, we focus on specific interactions of CLL cells with the microenvironmental component, as they occur through the usage by CLL cells of specific molecular structures whose expression has been associated with prognosis, including: i) interactions of CLL cells via the surface BCR and dependent on specific molecular features of the BCR itself and/or the presence of the BCR-associated molecule ZAP-70; ii) non-BCR-dependent proliferative and/or pro-survival interactions of CLL cells by CD49d and CD38. An overview of the putative drugs that could be employed to target specific molecules involved in CLL cells/tumor microenvironment interactions is also proposed in the closing chapter of the review.

Original languageEnglish
Pages (from-to)3323-3334
Number of pages12
JournalCurrent Pharmaceutical Design
Volume18
Issue number23
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Chronic lymphocytic leukemia
  • Microenvironment
  • Therapy

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

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