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| 001 | 148858 | ||
| 005 | 20240229112709.0 | ||
| 024 | 7 | _ | |a 10.1182/blood.2019001187 |2 doi |
| 024 | 7 | _ | |a pmid:31527074 |2 pmid |
| 024 | 7 | _ | |a 0006-4971 |2 ISSN |
| 024 | 7 | _ | |a 1528-0020 |2 ISSN |
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| 037 | _ | _ | |a DKFZ-2020-00050 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Chapiro, Elise |b 0 |
| 245 | _ | _ | |a Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53. |
| 260 | _ | _ | |a Stanford, Calif. |c 2019 |b HighWire Press |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1577971891_11608 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a B-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessments of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex (≥3 abnormalities) in 73% of the patients and highly complex (≥5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving MYC [t(MYC)] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six (76%) of the 34 patients exhibited an MYC aberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in TP53, MYD88, BCOR, MYC, SF3B1, SETD2, CHD2, CXCR4, and BCLAF1. The majority of B-PLL used the IGHV3 or IGHV4 subgroups (89%) and displayed significantly mutated IGHV genes (79%). We identified 3 distinct cytogenetic risk groups: low risk (no MYC aberration), intermediate risk (MYC aberration but no del17p), and high risk (MYC aberration and del17p) (P = .0006). In vitro drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif inhibitor targeting MYC) was associated with significantly lower viability of B-PLL cells harboring a t(MYC). We concluded that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting MYC may be a useful treatment option in this disease. |
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| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 700 | 1 | _ | |a Pramil, Elodie |b 1 |
| 700 | 1 | _ | |a Diop, M'boyba |b 2 |
| 700 | 1 | _ | |a Roos-Weil, Damien |b 3 |
| 700 | 1 | _ | |a Dillard, Clémentine |b 4 |
| 700 | 1 | _ | |a Gabillaud, Clémentine |b 5 |
| 700 | 1 | _ | |a Maloum, Karim |b 6 |
| 700 | 1 | _ | |a Settegrana, Catherine |b 7 |
| 700 | 1 | _ | |a Baseggio, Lucile |b 8 |
| 700 | 1 | _ | |a Lesesve, Jean-François |b 9 |
| 700 | 1 | _ | |a Yon, Mélanie |b 10 |
| 700 | 1 | _ | |a Jondreville, Ludovic |b 11 |
| 700 | 1 | _ | |a Lesty, Claude |b 12 |
| 700 | 1 | _ | |a Davi, Frédéric |b 13 |
| 700 | 1 | _ | |a Le Garff-Tavernier, Magali |b 14 |
| 700 | 1 | _ | |a Droin, Nathalie |b 15 |
| 700 | 1 | _ | |a Dessen, Philippe |b 16 |
| 700 | 1 | _ | |a Algrin, Caroline |b 17 |
| 700 | 1 | _ | |a Leblond, Véronique |b 18 |
| 700 | 1 | _ | |a Gabarre, Jean |b 19 |
| 700 | 1 | _ | |a Bouzy, Simon |b 20 |
| 700 | 1 | _ | |a Eclache, Virginie |b 21 |
| 700 | 1 | _ | |a Gaillard, Baptiste |b 22 |
| 700 | 1 | _ | |a Callet-Bauchu, Evelyne |b 23 |
| 700 | 1 | _ | |a Muller, Marc |b 24 |
| 700 | 1 | _ | |a Lefebvre, Christine |b 25 |
| 700 | 1 | _ | |a Nadal, Nathalie |b 26 |
| 700 | 1 | _ | |a Ittel, Antoine |b 27 |
| 700 | 1 | _ | |a Struski, Stéphanie |b 28 |
| 700 | 1 | _ | |a Collonge-Rame, Marie-Agnès |b 29 |
| 700 | 1 | _ | |a Quilichini, Benoit |b 30 |
| 700 | 1 | _ | |a Fert-Ferrer, Sandra |b 31 |
| 700 | 1 | _ | |a Auger, Nathalie |b 32 |
| 700 | 1 | _ | |a Radford-Weiss, Isabelle |b 33 |
| 700 | 1 | _ | |a Wagner, Lena |b 34 |
| 700 | 1 | _ | |a Scheinost, Sebastian |0 P:(DE-He78)648d23797edea029cdadba96810a9e8c |b 35 |u dkfz |
| 700 | 1 | _ | |a Zenz, Thorsten |b 36 |
| 700 | 1 | _ | |a Susin, Santos A |b 37 |
| 700 | 1 | _ | |a Bernard, Olivier A |b 38 |
| 700 | 1 | _ | |a Nguyen-Khac, Florence |b 39 |
| 773 | _ | _ | |a 10.1182/blood.2019001187 |g Vol. 134, no. 21, p. blood.2019001187 |0 PERI:(DE-600)1468538-3 |n 21 |p 1821-1831 |t Blood |v 134 |y 2019 |x 1528-0020 |
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