TCRα rearrangements identify a subgroup of NKL-deregulated adult T-ALLs associated with favorable outcome View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-01

AUTHORS

P Villarese, C Lours, A Trinquand, S Le Noir, M Belhocine, L Lhermitte, A Cieslak, M Tesio, A Petit, M LeLorch, S Spicuglia, N Ifrah, H Dombret, A W Langerak, N Boissel, E Macintyre, V Asnafi

ABSTRACT

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. More... »

PAGES

61

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/leu.2017.176

    DOI

    http://dx.doi.org/10.1038/leu.2017.176

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1085935900

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28592888


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