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The impact of the tissue microenvironment on the microRNAs in chronic lymphocytic leukemia

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The role of the microenvironment in leukaemia progression

Chronic lymphocytic leukaemia (CLL) presents with clinical heterogeneity. Understanding the genetic basis for variable progression of CLL could lead to more effective therapies.

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CLL is the most diffuse form of leukaemia and usually becomes diagnosed in the indolent stage. Although most patients may never require therapy, approximately 30-40 % progress to a more advanced clinical stage and ultimately die from the disease. Therefore, there is an urgent need to identify genes implicated in disease progression. CLL cells avoid apoptosis and acquire better growing conditions following antigenic stimulation and interaction in tissues. Researchers of the EU-funded VIMIRNASCLL (The impact of the tissue microenvironment on the microRNAs in chronic lymphocytic leukemia) project investigated how the microenvironment could influence CLL progression by deregulating microRNAs. For this purpose, they isolated CLL cells from the bone marrow, lymph nodes and peripheral blood and evaluated the expression of selected microRNAs in B-cells after cell-cell mediated interaction. Experimental evidence indicated that miR-181b, known for its role in the active cross-talk between B and T cells, was low in CLL B cells. This translated into apoptosis evasion in CLL cells as well as escape from cytotoxic T cell killing. Additionally, scientists discovered that transcriptional regulation of miR-15a/16-1 affected CLL cell cycle and apoptosis. They speculated that the random loss of one of the miR-15a/16-1 alleles in CLL might distinguish the aggressive from the indolent form of the disease. Collectively, the VIMIRNASCLL study findings supported the rationale that CLL progression depends on environmental cues and microRNA deregulation is triggered by specific cellular cross-talk stimuli. The generated information could be used to develop new microRNA-based anti-cancer therapies that improve clinical management of CLL patients.

Keywords

Microenvironment, chronic lymphocytic leukaemia, VIMIRNASCLL, miR-181b, miR-15a/16-1

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