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Genetic analysis of the largest ever cohort of B-PLL patients

These results, published in Blood by Florence Nguyen-Khac and her team, allow for diagnosis and prognosis of B-PLL, a rare lymphoid leukemia so far difficult to diagnose and treat.

First demonstration of diagnostic and prognostic

markers of prolymphocytic B leukemia.


Prolymphocytic B leukemia (PBL) is a disease that affects B lymphocytes and has long been an object of controversy among physicians, being either classified as aggressive chronic lymphocytic leukemia or mantle cell lymphoma. It is a rare disease, little studied, rapidly progressive, with no known prognostic factors, difficult to diagnose, and mainly affects the elderly.

Florence Nguyen-Khac's team was able to study a cohort of 34 patients with LPLB, the largest cohort described to date. The researchers studied the cellular, genetic and molecular characteristics of these patients.  Through cytogenetic analyses and high-throughput sequencing, they showed that LPLB presents a particular pattern of genomic abnormalities, distinct from other B blood diseases, with frequent abnormalities of the MYC (activation) and TP53 (inactivation) genes, two genes often involved in blood cancers (leukemias) and lymph node cancers (lymphomas). In addition, these results indicate that the concomitant presence of abnormalities in these two genes corresponds to a very poor prognosis.

In addition, the researchers tested a combination of drugs targeting the myc gene, and showed that these drugs can specifically kill LPLB cells carrying a certain type of myc gene abnormality (translocation). These results therefore open up prospects for the treatment of these leukaemias.

In conclusion, F. Nguyen-Khac's team has shown that LPLB has a particular genomic profile, different from other mature B haemopathies, and thus confirms the need to distinguish it in the World Health Organization (WHO) classification. The researchers recommend that cytogenetic analysis (karyotype and fluorescent in situ hybridization) should be performed in any patient with a hard-to-classify hemopathy B. These analyses would make it possible both to diagnose the type of haemopathy the patient suffers from and to adapt treatment according to the genetic characteristics identified.

These results were published at the end of November in the journal Blood (1) , the best haematology journal (IF: 16.5), and were accompanied by a commentary article stressing the importance of this work (2).


1. 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 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, Nguyen-Khac F. Blood. 2019 Nov 21;134(21):1821-1831
Article in pdf

2. B-cell prolymphocytic leukemia has 3 subsets. Kay NE and Hanson CA. Blood 2019. PMID 31751477

Comment in pdf

Contact:

Florence NGUYEN-KHAC, PU-PH (email)

Team Cell death and drug resistance in hematological disorders

 

Legend: B prolymphocytes (purple-stained cells) make up at least 55% of the lymphoid cells in the blood in patients with BPL.

 

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