{"id":1760,"date":"2019-12-12T11:27:20","date_gmt":"2019-12-12T10:27:20","guid":{"rendered":"https:\/\/curamus-cancer.fr\/caracterisation-genomique-de-la-leucemie-prolymphocytaire-b-un-modele-hierarchique-pronostique-impliquant-les-genes-myc-et-tp53\/"},"modified":"2020-05-10T13:20:40","modified_gmt":"2020-05-10T11:20:40","slug":"genetic-characterization-of-b-cell-prolymphocytic-leukemia-a-prognostic-model-involving-myc-and-tp53","status":"publish","type":"post","link":"https:\/\/curamus-cancer.fr\/en\/genetic-characterization-of-b-cell-prolymphocytic-leukemia-a-prognostic-model-involving-myc-and-tp53\/","title":{"rendered":"Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53"},"content":{"rendered":"<h1>Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53<\/h1>\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31527074\">Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53.<\/a><\/p>\n<p><em>Chapiro E, Pramil E, Diop M, Roos-Weil D, Dillard C, Gabillaud C, Maloum K, Settegrana C, Baseggio L, Lesesve JF, 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 MA, Quilichini B, Fert-Ferrer S, Auger N, Radford-Weiss I, Wagner L, Scheinost S, Zenz T, Susin SA, Bernard OA, <strong>Nguyen-Khac F<\/strong>. Blood. 2019 Nov 21;134(21):1821-1831<\/em><\/p>\n<p>This work has just been published in Blood (n\u00b01 journal in Hematology). The article has been selected for an editorial commentary and for an international CME (continuing medical education) training course. This work had been selected for oral communication at the last annual American International Congress (ASH). This is the world&#8217;s largest series of an aggressive form of chronic lymphocytic leukemia: B prolymphocytic leukemia.<\/p>\n<p>Prolymphocytic B leukemia (PBL) has been a long debated entity within mature B-hematopathies, often being classified as either aggressive chronic lymphocytic leukemia or mantle cell lymphoma. It is a rare, poorly studied haemopathy, affecting the elderly, with a rapid progression and no known prognostic factor. Diagnosis is difficult because cytology is based on the presence of prolymphocytes representing more than 55% of blood lymphoid cells.<\/p>\n<p>We report here a cytogenetic and molecular study of a national series of 34 LPLB, the largest described to date. The cytological diagnosis was reviewed by 3 experts independently. We showed that LPLB was often associated with a complex (&gt; 3 chromosomal abnormalities) and very complex (&gt; 5 abnormalities) karyotype (73% and 45% respectively). The most frequent chromosomal abnormalities were translocations involving the MYC [t(MYC)] gene (62%), deletion (del) 17p (involving the TP53 gene) (38%), trisomy (sorting) 18 (30%), del13q (29%), tri3 (24%), tri12 (24%) and del8p (23%). A large majority of patients (76%) had MYC aberration, either by translocation or gain (14%), these two abnormalities being mutually exclusive. Sequencing of the exomes revealed recurrent mutations in the TP53, MYD88, BCOR, MYC, SF3B1, SETD2, CHD2, CXCR4 and BCLAF1 genes. The majority of the LPLBs (89%) used the IGHV3 or IGHV4 genes preferentially, and expressed mutated IGHVs (79%).<\/p>\n<p>We propose a hierarchical model with 3 cytogenetic groups: low risk (no MYC anomaly), intermediate (MYC anomaly without del17p), and high risk with double hit (MYC anomaly and del17p) with the shortest survival (p=0.0006).<\/p>\n<p>Finally, we tested the combination bcl2 inhibitor + OTX015 (bromodomain inhibitor and extraterminal motif targeting MYC) on primary samples in in vitro experiments, and concluded that these drugs can induce the death of LPLB cells with t(MYC) translocation.<\/p>\n<p>&nbsp;<\/p>\n<blockquote><p>In total, we show that LPLB has a particular genomic profile, different from other mature B-haemopathies, and confirm the need to distinguish it in the World Health Organization (WHO) classification. We recommend that cytogenetic analysis (karyotype and fluorescent in situ hybridization) be performed in any patient with a difficult-to-classify B hemopathy.\u00a0 On the one hand it is an important diagnostic aid and on the other hand it is an important prognostic factor.<\/p><\/blockquote>\n<p><a href=\"https:\/\/curamus-cancer.fr\/wp-content\/uploads\/2019\/12\/B-PLL.jpg\"><img decoding=\"async\" class=\"wp-image-1301 aligncenter lazyload\" data-src=\"https:\/\/curamus-cancer.fr\/wp-content\/uploads\/2019\/12\/B-PLL.jpg\" alt=\"\" width=\"745\" height=\"370\" data-srcset=\"https:\/\/curamus-cancer.fr\/wp-content\/uploads\/2019\/12\/B-PLL.jpg 972w, https:\/\/curamus-cancer.fr\/wp-content\/uploads\/2019\/12\/B-PLL-300x149.jpg 300w, https:\/\/curamus-cancer.fr\/wp-content\/uploads\/2019\/12\/B-PLL-768x382.jpg 768w\" data-sizes=\"(max-width: 745px) 100vw, 745px\" src=\"data:image\/svg+xml;base64,PHN2ZyB3aWR0aD0iMSIgaGVpZ2h0PSIxIiB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciPjwvc3ZnPg==\" style=\"--smush-placeholder-width: 745px; --smush-placeholder-aspect-ratio: 745\/370;\" \/><\/a><\/p>\n<p>More information :<\/p>\n<p><a href=\"https:\/\/curamus-cancer.fr\/wp-content\/uploads\/2019\/12\/bpll-blood-nov-2019.pdf\">bpll blood nov 2019<\/a><\/p>\n<p><a href=\"https:\/\/curamus-cancer.fr\/wp-content\/uploads\/2019\/12\/BPLL-comment-blood-nov-2019.pdf\">BPLL comment blood nov 2019<\/a><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Synthesis for the general public<\/strong><\/p>\n<blockquote><p>Prolymphocytic B leukemia (PBLL) has been a long debated entity within mature B haemopathies, often being classified as either aggressive chronic lymphocytic leukemia or mantle cell lymphoma. It is a rare, poorly studied, elderly hemopathy, with a rapid progression, no known prognostic factor, and difficult to diagnose.<\/p>\n<p>With cytogenetic analyses and high-throughput sequencing, we have shown that LPLB has a particular profile of genomic abnormalities, distinct from other B haemopathies, with frequent abnormalities of the MYC (activation) and TP53 (inactivation) genes, two genes frequently involved in blood (leukaemia) and lymph node (lymphoma) cancers. In addition, we showed that when these two genes were abnormal concomitantly, the prognosis was unfavourable. Finally, the combination of molecules including drugs targeting the MYC gene could be a lead to treat certain LPLB. We propose to perform a cytogenetic analysis on all difficult-to-classify B-haemopathies, as it is a simple to perform analysis that is important for diagnosis and prognosis.<\/p><\/blockquote>\n<p style=\"text-align: right;\"><strong>Pr Florence Nguyen-Khac<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53 Genetic characterization of B-cell prolymphocytic leukemia: a [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":1761,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[27],"tags":[],"class_list":["post-1760","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-leucemie-vulgarise-en-2"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53 - 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