TCRα rearrangements identify a subgroup of NKL-deregulated adult T-ALLs associated with favorable outcome
| Autor: | Mohamed Belhocine, Audrey Petit, Patrick Villarese, S Le Noir, C Lours, Anthonie Willem Langerak, M. Tesio, M. Lelorc’h, A Cieslak, Vahid Asnafi, Norbert Ifrah, Elizabeth Macintyre, Nicolas Boissel, Salvatore Spicuglia, Ludovic Lhermitte, Amélie Trinquand, Hervé Dombret |
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| Přispěvatelé: | Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Technologies avancées pour le génôme et la clinique ( TAGC ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunology |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research Lineage (genetic) Receptors Antigen T-Cell alpha-beta T cell Cellular differentiation [SDV]Life Sciences [q-bio] Biology Precursor T-Cell Lymphoblastic Leukemia-Lymphoma 03 medical and health sciences Antigen Cell Line Tumor medicine Humans Leukemia-Lymphoma Adult T-Cell Receptor Gene ComputingMilieux_MISCELLANEOUS Homeodomain Proteins [ SDV ] Life Sciences [q-bio] T-cell receptor Cell Differentiation Receptors Antigen T-Cell gamma-delta Hematology Molecular biology 030104 developmental biology medicine.anatomical_structure Oncology Female Ectopic expression HeLa Cells |
| Zdroj: | Leukemia Leukemia, 2017, 〈10.1038/leu.2017.176〉 Leukemia, 2017, ⟨10.1038/leu.2017.176⟩ Leukemia, 32(1), 61-71. Nature Publishing Group |
| ISSN: | 0887-6924 1476-5551 |
| Popis: | T-cell acute lymphoblastic leukemia (T-ALL) results from leukemic transformation of T-cell precursors arrested at specific differentiation stages, including an 'early-cortical' thymic maturation arrest characterized by expression of cytoplasmic TCRβ but no surface T-cell receptor (TCR) and frequent ectopic expression of the TLX1/3 NK-like homeotic proteins (NKL). We designed a TCRα VJC PCR to identify clonal TCRα rearrangements in 32% of 127 T-ALLs, including 0/52 immature/TCRγδ lineage cases and 41/75 (55%) TCRαβ lineage cases. Amongst the latter, TCRα rearrangements were not identified in 30/54 (56%) of IMβ/pre-αβ early-cortical T-ALLs, of which the majority (21/30) expressed TLX1/3. We reasoned that the remaining T-ALLs might express other NKL proteins, so compared transcript levels of 46 NKL in T-ALL and normal thymic subpopulations. Ectopic overexpression of 10 NKL genes, of which six are unreported in T-ALL (NKX2-3, BARHL1, BARX2, EMX2, LBX2 and MSX2), was detectable in 17/104 (16%) T-ALLs. Virtually all NKL overexpressing T-ALLs were TCRα unrearranged and ectopic NKL transcript expression strongly repressed Eα activity, suggesting that ectopic NKL expression is the major determinant in early-cortical thymic T-ALL maturation arrest. This immunogenetic T-ALL subtype, defined by TCRβ VDJ but no TCRα VJ rearrangement, is associated with a favorable outcome in GRAALL-treated adult T-ALLs. |
| Databáze: | OpenAIRE |
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