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  • Title: IGHV unmutated CLL B cells are more prone to spontaneous apoptosis and subject to environmental prosurvival signals than mutated CLL B cells.
    Author: Coscia M, Pantaleoni F, Riganti C, Vitale C, Rigoni M, Peola S, Castella B, Foglietta M, Griggio V, Drandi D, Ladetto M, Bosia A, Boccadoro M, Massaia M.
    Journal: Leukemia; 2011 May; 25(5):828-37. PubMed ID: 21372840.
    Abstract:
    Tumor cells in chronic lymphocytic leukemia (CLL) are more prone to apoptosis when cultured ex vivo, because they lack prosurvival signals furnished in vivo via B-cell receptor (BCR)-dependent and -independent pathways. This study compared the susceptibility of unmutated (UM) and mutated (M) CLL B cells to spontaneous apoptosis and prosurvival signals. UM CLL B cells showed a significantly higher rate of spontaneous apoptosis than M CLL B cells. Nuclear factor-kB (NF-kB) was rapidly inactivated, and B-cell leukemia/lymphoma 2 (Bcl-2) expression progressively down-regulated in the UM CLL B cells. CD40-Ligand, interleukin-4 and stromal cells significantly improved their viability and partially recovered Bcl-2, but not NF-kB expression. Peripheral blood mononuclear cells also offered protection of UM CLL B cells, and recovered both NF-kB and Bcl-2 expression. T cells, rather than nurse-like cells, were responsible for protecting UM CLL B cells by means of cell-to-cell contact and soluble factors. Despite their more aggressive features, UM CLL B cells are more susceptible to spontaneous apoptosis and depend from environmental prosurvival signals. This vulnerability of UM CLL B cells can be exploited as a selective target of therapeutic interventions.
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