This section shows a general overview of information for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- Reference
- Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53.
- Paper ID
- COSP47139
- Authors
- Affiliation
- AP-HP, France.
- Journal
-
Blood, 2019
ISSN: 1528-0020
PMID: 31527074 (view at PubMed or Europe PMC) - Abstract
- B-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessment of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex ({greater than or equal to}3 abnormalities) in 73% of the patients and highly complex (<u>></u>5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving <i>MYC</i> [t(<i>MYC</i>)] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six of the 34 patients (76%) exhibit <i>MYC</i> aberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in <i>TP53</i>, <i>MYD88</i>, <i>BCOR</i>, <i>MYC</i>, <i>SF3B1</i>, <i>SETD2</i>, <i>CHD2</i>, <i>CXCR4</i>, and <i>BCLAF1</i> The majority of B-PLL used the <i>IGHV3</i> or <i>IGHV4</i> subgroups (89%), and displayed significantly mutated <i>IGHV</i> genes (79%). We identified three distinct cytogenetic risk groups: low-risk (no <i>MYC</i> aberration), intermediate-risk (<i>MYC</i> aberration but no del17p), and high-risk (<i>MYC</i> aberration and del17p) (p=.0006). <i>In vitro</i> drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif (BET) inhibitor targeting <i>MYC</i>) was associated with significantly lower viability of B-PLL cells harboring a t(<i>MYC</i>). We conclude that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting <i>MYC</i> may be a useful treatment option in this disease.
- Paper Status
- Curated
- Genes Analysed
- 1012
- Mutated Samples
- 16
- Total No. of Samples
- 16