Journal Article

DKFZ-2020-00050

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53.

Chapiro, E. ; Pramil, E. ; Diop, M. ; Roos-Weil, D. ; Dillard, C. ; Gabillaud, C. ; Maloum, K. ; Settegrana, C. ; Baseggio, L. ; Lesesve, J.-F. ; Yon, M. ; Jondreville, L. ; Lesty, C. ; Davi, F. ; Le Garff-Tavernier, M. ; Droin, N. ; Dessen, P. ; Algrin, C. ; Leblond, V. ; Gabarre, J. ; Bouzy, S. ; Eclache, V. ; Gaillard, B. ; Callet-Bauchu, E. ; Muller, M. ; Lefebvre, C. ; Nadal, N. ; Ittel, A. ; Struski, S. ; Collonge-Rame, M.-A. ; Quilichini, B. ; Fert-Ferrer, S. ; Auger, N. ; Radford-Weiss, I. ; Wagner, L. ; Scheinost, S.DKFZ* ; Zenz, T. ; Susin, S. A. ; Bernard, O. A. ; Nguyen-Khac, F.

2019
HighWire Press Stanford, Calif.

This record in other databases:  

Please use a persistent id in citations: doi:10.1182/blood.2019001187

Abstract: 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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Contributing Institute(s):

1. Molekulare Therapie in der Hämatologie und Onkologie (G250)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 15 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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