T-cell-directed TAL-1 expression induces T-cell malignancies in transgenic mice

G. L. Condorelli, F. Facchiano, M. Valtieri, E. Proietti, L. Vitelli, V. Lulli, K. Huebner, C. Peschle, C. M. Croce

Research output: Contribution to journalArticlepeer-review

Abstract

The TAL-1 gene specifies for a basic domain-helix-loop-helix protein, which is involved in the control of normal hematopoiesis. In human pathology, the TAL-1 gene product is expressed in a high percentage of T-cell acute lymphoblastic leukemias in the pediatric age range; however, it has not been established whether the expression has a causal role in oncogenesis. In this report, we describe the phenotype of mouse transgenic lines obtained by inducing tal-1 protein expression in lymphoid tissues using the LCK promoter. The survival rate of tal-1 transgenic animals was much lower as compared with control mice. Histopathological analysis revealed lymphomas of T-cell type, often comprising a minor B-cell component. Some mice showed marked splenic lymphocyte depletion. Primary lymphocyte cultures showed partial independence from exogenous growth stimuli and increased resistance to low-serum apoptosis. To further unravel the tal-1 oncogenic potential, a strain of tal- 1 transgenic mice was crossbred with p53(-/-) mice; the survival rate in these animals was reduced by more than one-half when compared with that of tal-1 mice, and histopathological analysis revealed exclusively T-cell lymphomas. These data indicate that TAL-1, expressed in T cells, is per sea potent oncogene, which may exert a key leukemogenetic role in the majority of T-cell acute lymphoblastic leukemias.

Original languageEnglish
Pages (from-to)5113-5119
Number of pages7
JournalCancer Research
Volume56
Issue number22
Publication statusPublished - Nov 15 1996

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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