Differential gene expression induction by TRAIL in B chronic lymphocytic leukemia (B-CLL) cells showing high versus low levels of Zap-70

Paola Secchiero, Maria Grazia Di Iasio, Arianna Gonelli, Elisa Barbarotto, Elisabetta Melloni, Mario Tiribelli, Cristina Chiaruttini, Giorgio Zauli

Research output: Contribution to journalArticle

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Abstract

Among 14 peripheral blood samples obtained from patients affected by B chronic lymphocytic leukemia (B-CLL) at initial stages (Rai 0-1) of the disease, 6 showed intermediate/high levels of Zap-70 while 8 displayed low/absent levels of Zap-70. Although Zap-70high and Zap-70low B-CLL samples displayed similar levels of surface death receptor TRAIL-R2, recombinant TRAIL induced cytotoxicity only in a subset of Zap-70low B-CLL samples while Zap-70high were completely resistant to TRAIL. The gene expression profiling was next analyzed in all B-CLL samples treated with either chlorambucil or recombinant TRAIL. While chlorambucil up-regulated the steady-state mRNA levels of known p53 target genes, such as PUMA, Fas/CD95 and MDM2 in all B-CLL samples examined, it significantly down-regulated survivin in Zap-70low but not in Zap-70high. On the other hand, recombinant TRAIL up-regulated the expression of several cytokines (IL-1β, IL-1α, IL-8), which have been involved in promoting B-CLL cell survival. In particular, TRAIL selectively up-regulated IL-1β in Zap-70low B-CLL samples, while it markedly and selectively up-regulated its own mRNA and that of cyclooxigenase-2 (COX-2) in Zap-70high. Taken together, our findings suggest that a significant expression of Zap-70 modulate the response of B-CLL to TRAIL, which might represents an initial step in the pathogenesis of B-CLL.

Original languageEnglish
Pages (from-to)229-236
Number of pages8
JournalJournal of Cellular Physiology
Volume213
Issue number1
DOIs
Publication statusPublished - Oct 2007

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B-Cell Chronic Lymphocytic Leukemia
Interleukin-1
Gene expression
Chlorambucil
Gene Expression
Death Domain Receptors
Messenger RNA
Cytotoxicity
Interleukin-8
Blood
Genes
Cells
Cytokines
p53 Genes
Gene Expression Profiling
Cell Survival

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Differential gene expression induction by TRAIL in B chronic lymphocytic leukemia (B-CLL) cells showing high versus low levels of Zap-70. / Secchiero, Paola; Di Iasio, Maria Grazia; Gonelli, Arianna; Barbarotto, Elisa; Melloni, Elisabetta; Tiribelli, Mario; Chiaruttini, Cristina; Zauli, Giorgio.

In: Journal of Cellular Physiology, Vol. 213, No. 1, 10.2007, p. 229-236.

Research output: Contribution to journalArticle

Secchiero, P, Di Iasio, MG, Gonelli, A, Barbarotto, E, Melloni, E, Tiribelli, M, Chiaruttini, C & Zauli, G 2007, 'Differential gene expression induction by TRAIL in B chronic lymphocytic leukemia (B-CLL) cells showing high versus low levels of Zap-70', Journal of Cellular Physiology, vol. 213, no. 1, pp. 229-236. https://doi.org/10.1002/jcp.21116
Secchiero, Paola ; Di Iasio, Maria Grazia ; Gonelli, Arianna ; Barbarotto, Elisa ; Melloni, Elisabetta ; Tiribelli, Mario ; Chiaruttini, Cristina ; Zauli, Giorgio. / Differential gene expression induction by TRAIL in B chronic lymphocytic leukemia (B-CLL) cells showing high versus low levels of Zap-70. In: Journal of Cellular Physiology. 2007 ; Vol. 213, No. 1. pp. 229-236.
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AU - Secchiero, Paola

AU - Di Iasio, Maria Grazia

AU - Gonelli, Arianna

AU - Barbarotto, Elisa

AU - Melloni, Elisabetta

AU - Tiribelli, Mario

AU - Chiaruttini, Cristina

AU - Zauli, Giorgio

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AB - Among 14 peripheral blood samples obtained from patients affected by B chronic lymphocytic leukemia (B-CLL) at initial stages (Rai 0-1) of the disease, 6 showed intermediate/high levels of Zap-70 while 8 displayed low/absent levels of Zap-70. Although Zap-70high and Zap-70low B-CLL samples displayed similar levels of surface death receptor TRAIL-R2, recombinant TRAIL induced cytotoxicity only in a subset of Zap-70low B-CLL samples while Zap-70high were completely resistant to TRAIL. The gene expression profiling was next analyzed in all B-CLL samples treated with either chlorambucil or recombinant TRAIL. While chlorambucil up-regulated the steady-state mRNA levels of known p53 target genes, such as PUMA, Fas/CD95 and MDM2 in all B-CLL samples examined, it significantly down-regulated survivin in Zap-70low but not in Zap-70high. On the other hand, recombinant TRAIL up-regulated the expression of several cytokines (IL-1β, IL-1α, IL-8), which have been involved in promoting B-CLL cell survival. In particular, TRAIL selectively up-regulated IL-1β in Zap-70low B-CLL samples, while it markedly and selectively up-regulated its own mRNA and that of cyclooxigenase-2 (COX-2) in Zap-70high. Taken together, our findings suggest that a significant expression of Zap-70 modulate the response of B-CLL to TRAIL, which might represents an initial step in the pathogenesis of B-CLL.

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