title: Ectopic expression of TAL-1 protein in Ly-6E.1-htal-1 transgenic mice induces defects in B- and T-lymphoid differentiation.
abstract: 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.
authors.affiliation: Institut Cochin, Département d'Hématologie, INSERM, CNRS, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goardon
authors.forename: Annette
authors.initials: A
authors.lastname: Schuh
authors.forename: Iman
authors.initials: I
authors.lastname: Hajar
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Ma
authors.forename: Hélène
authors.initials: H
authors.lastname: Jouault
authors.forename: Elaine
authors.initials: E
authors.lastname: Dzierzak
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Roméo
authors.forename: Leïla
authors.initials: L
authors.lastname: Maouche-Chrétien
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects; D015458:Leukemia, T-Cell / Q000209:etiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D000950:Antigens, Ly; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C074650:Ly6a protein, mouse; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human