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Fasseu M, Aplan PD, Chopin M, et al. p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis. Blood. 2007;110(7):2610-9doi: 10.1182/blood-2007-01-066209.
Fasseu, M., Aplan, P. D., Chopin, M., Boissel, N., Bories, J. C., Soulier, J., von Boehmer, H., Sigaux, F., & Regnault, A. (2007). p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis. Blood, 110(7), 2610-9. https://doi.org/10.1182/blood-2007-01-066209
Fasseu, Magali, et al. "p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis." Blood vol. 110,7 (2007): 2610-9. doi: https://doi.org/10.1182/blood-2007-01-066209
Fasseu M, Aplan PD, Chopin M, Boissel N, Bories JC, Soulier J, von Boehmer H, Sigaux F, Regnault A. p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis. Blood. 2007 Oct 01;110(7):2610-9. doi: 10.1182/blood-2007-01-066209. Epub 2007 May 16. PMID: 17507663; PMCID: PMC1988920.
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Blood. 2007 Oct 01;110(7):2610-9. doi: 10.1182/blood-2007-01-066209. Epub 2007 May 16.

p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis.

Blood

Magali Fasseu, Peter D Aplan, Martine Chopin, Nicolas Boissel, Jean-Christophe Bories, Jean Soulier, Harald von Boehmer, François Sigaux, Armelle Regnault

Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (INSERM) U462, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.

PMID: 17507663 PMCID: PMC1988920 DOI: 10.1182/blood-2007-01-066209

Abstract

Inactivation of the CDKN2 genes that encode the p16(INK4A) and p14(ARF) proteins occurs in the majority of human T-cell acute lymphoblastic leukemias (T-ALLs). Ectopic expression of TAL1 and LMO1 genes is linked to the development of T-ALL in humans. In TAL1xLMO1 mice, leukemia develops in 100% of mice at 5 months. To identify the molecular events crucial to leukemic transformation, we produced several mouse models. We report here that expression of P16(INK4A) in developing TAL1xLMO1 thymocytes blocks leukemogenesis in the majority of the mice, and the leukemias that eventually develop show P16(INK4A) loss of expression. Events related to the T-cell receptor beta selection process are thought to be important for leukemic transformation. We show here that the absence of the pTalpha chain only slightly delays the appearance of TAL1xLMO1-induced T-ALL, which indicates a minor role of the pTalpha chain. We also show that the CD3epsilon-mediated signal transduction pathway is essential for this transformation process, since the TAL1xLMO1xCD3epsilon-deficient mice do not develop T-ALL for up to 1 year.

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