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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.

Type

Journal article

Journal

Blood

Publication Date

15/07/2002

Volume

100

Pages

491 - 500

Keywords

Animals, Antigens, Ly, B-Lymphocytes, Basic Helix-Loop-Helix Transcription Factors, Bone Marrow Transplantation, Cell Differentiation, Cell Lineage, DNA-Binding Proteins, Gene Expression Regulation, Genetic Vectors, Hematopoiesis, Hematopoietic Stem Cells, Humans, Immunoglobulin Class Switching, Leukemia, T-Cell, Membrane Proteins, Mice, Mice, SCID, Mice, Transgenic, Proto-Oncogene Proteins, T-Cell Acute Lymphocytic Leukemia Protein 1, T-Lymphocytes, Transcription Factors