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Blood, 15 July 2002, Vol. 100, No. 2, pp. 491-500

HEMATOPOIESIS

Ectopic expression of TAL-1 protein in Ly-6E.1-htal-1 transgenic mice induces defects in B- and T-lymphoid differentiation

Nicolas Goardon, Annette Schuh, Iman Hajar, Xiaoqian Ma, Hélène Jouault, Elaine Dzierzak, Paul-Henri Roméo, and Leïla Maouche-Chrétien

From the Institut Cochin, Département d'Hématologie, INSERM, CNRS, Paris, France; the Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands; and the Département d'Hématologie, Hôpital Henri Mondor, Créteil, France.

The tal-1 gene encodes a basic helix-loop-helix (bHLH) transcription factor required for primitive and definitive hematopoiesis. Additionally, ectopic activation of the tal-1 gene during T lymphopoiesis occurs in numerous cases of human T-cell acute lymphoblastic leukemia. With the use of transgenic mice, we show that, in adult hematopoiesis, constitutive expression of TAL-1 protein causes disorders in the hematopoietic lineages that normally switch off tal-1 gene expression during their differentiation process. Myelopoiesis was characterized by a moderate increase of myeloid precursors and by Sca-1 antigen persistence. Although no lymphoid leukemia was observed, T lymphopoiesis and B lymphopoiesis were severely impaired. Transgenic mice showed reduced thymic cellularity together with a decrease in double-positive cells and a concurrent increase in the single-positive population. B cells exhibited a differentiation defect characterized by a reduction of the B-cell compartment most likely because of a differentiation block upstream of the intermediate pro-B progenitor. B cells escaping this defect developed normally, but transgenic splenocytes presented a defect in immunoglobulin class switch recombination. Altogether, these results enlighten the fine-tuning of TAL-1 expression during adult hematopoiesis and indicate why TAL-1 expression has to be switched off in the lymphoid lineages.

© 2002 by The American Society of Hematology.
 

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