IGHV unmutated CLL B cells are more prone to spontaneous apoptosis and subject to environmental prosurvival signals than mutated CLL B cells

被引：57

作者：

Coscia, M. ^{[1
,2
]}

Pantaleoni, F. ^{[2
]}

Riganti, C. ^{[3
]}

Vitale, C. ^{[1
,2
]}

Rigoni, M. ^{[2
]}

Peola, S. ^{[2
]}

Castella, B. ^{[2
]}

Foglietta, M. ^{[2
]}

Griggio, V. ^{[1
,2
]}

Drandi, D. ^{[1
]}

Ladetto, M. ^{[1
]}

Bosia, A. ^{[3
]}

Boccadoro, M. ^{[1
]}

Massaia, M. ^{[1
,2
]}

机构：

[1] Univ Turin, Div Ematol, Azienda Osped Univ San Giovanni Battista di Torin, I-10126 Turin, Italy

[2] Azienda Osped Univ San Giovanni Battista di Torin, Ctr Ric Med Sperimentale CeRMS, Lab Ematol Oncol, Turin, Italy

[3] Univ Turin, Dipartimento Genet Biol & Biochim, Turin, Italy

来源：

LEUKEMIA | 2011年 / 25卷 / 05期

关键词：

chronic lymphocytic leukemia; immunoglobulin mutational status; tumor microenvironment; CHRONIC LYMPHOCYTIC-LEUKEMIA; FACTOR-KAPPA-B; MARROW STROMAL CELLS; T-CELLS; THERAPEUTIC TARGET; CD38; EXPRESSION; NURSELIKE CELLS; IN-VITRO; SURVIVAL; PATHWAY;

D O I：

10.1038/leu.2011.12

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Leukemia (2011) 25, 828-837; doi: 10.1038/leu. 2011.12; published online 4 March 2011

引用

页码：828 / 837

页数：10

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