Cytogenetics in the management of mature B-cell non-Hodgkin lymphomas: Guidelines from the Groupe Francophone de Cytogénétique Hematologique (GFCH).

Non-Hodgkin lymphomas (NHL) consist of a wide range of clinically, phenotypically and genetically distinct neoplasms. The accurate diagnosis of mature B-cell non-Hodgkin lymphoma relies on a multidisciplinary approach that integrates morphological, phenotypical and genetic characteristics together with clinical features. Cytogenetic analyses remain an essential part of the diagnostic workup for mature B-cell lymphomas. Karyotyping is particularly useful to identify hallmark translocations, typical cytogenetic signatures as well as complex karyotypes, all bringing valuable diagnostic and/or prognostic information. Besides the well-known recurrent chromosomal abnormalities such as, for example, t(14;18)(q32;q21)/IGH::BCL2 in follicular lymphoma, recent evidences support a prognostic significance of complex karyotype in mantle cell lymphoma and Waldenström macroglobulinemia. Fluorescence In Situ Hybridization is also a key analysis playing a central role in disease identification, especially in genetically-defined entities, but also in predicting transformation risk or prognostication. This can be exemplified by the pivotal role of MYC, BCL2 and/or BCL6 rearrangements in the diagnostic of aggressive or large B-cell lymphomas. This work relies on the World Health Organization and the International Consensus Classification of hematolymphoid tumors together with the recent cytogenetic advances. Here, we review the various chromosomal abnormalities that delineate well-established mature B-cell non-Hodgkin lymphoma entities as well as newly recognized genetic subtypes and provide cytogenetic guidelines for the diagnostic management of mature B-cell lymphomas.

Discontinuation of tyrosine kinase inhibitor in chronic myeloid leukemia: a retrospective cohort in east occitania.

Tyrosine kinase inhibitor (TKI) discontinuation in chronic phase chronic myeloid leukemia (CML) patients has been examined in a real-life setting in the east occitania region of France. We have collected sex, age, prognostic scores, pre-TKI treatment, TKI length and response, relapse data from patients who had stopped TKI in prolonged complete molecular remission (CMR), and analyzed relapse risk factors. Sixty consecutive patients were included from january 2010 to december 2016. Sixteen received pre-TKI treatment. Fifty-three received a first-generation TKI, and seven had a second-generation TKI in first-line therapy. The median TKI time to achieve CMR was 20.5 months [5-137]. The median TKI length before discontinuation treatment was 73 months [12-158]. Twenty-two patients (37%) relapsed with a median time to relapse of 6 months [3-27]. An intermediate or high Sokal score was the only relapse risk factor (HR = 3.32, p < 0.05) associated with relapse after TKI discontinuation. TKI discontinuation was possible without relapse for half of the patients in chronic phase CML. In a real-life cohort, a high-risk Sokal score at diagnosis appears to be an adverse prognosis feature for TKI discontinuation.

Chromoanagenesis, the mechanisms of a genomic chaos.

Designated under the name of chromoanagenesis, the phenomena of chromothripsis, chromanasynthesis and chromoplexy constitute new types of complex rearrangements, including many genomic alterations localized on a few chromosomal regions, and whose discovery over the last decade has changed our perception about the formation of chromosomal abnormalities and their etiology. Although exhibiting specific features, these new catastrophic mechanisms generally occur within a single cell cycle and their emergence is closely linked to genomic instability. Various non-exclusive exogenous or cellular mechanisms capable of generating chromoanagenesis have been evoked. However, recent experimental data shed light on 2 major processes, which following a defect in the mitotic segregation of chromosomes, can generate a cascade of cellular events leading to chromoanagenesis. These mechanisms are the formation of micronuclei integrating isolated chromosomal material, and the occurrence of chromatin bridges around chromosomal material resulting from telomeric fusions. In both cases, the cellular and molecular mechanisms of fragmentation, repair and transmission of damaged chromosomal material are consistent with the features of chromoanagenesis-related complex chromosomal rearrangements. In this review, we introduce each type of chromoanagenesis, and describe the experimental models that have allowed to validate the existence of chromoanagenesis events and to better understand their cellular mechanisms of formation and transmission, as well as their impact on the stability and the plasticity of the genome.

[Extended-spectrum beta-lactamases-producing Stenotrophomonas maltophilia strains: CTX-M enzymes detection and virulence study]. / Etude de souches de Stenotrophomonas maltophilia sécrétrices de BLSE : détection de CTX-M et étude de la virulence.

OBJECTIVE: To study the beta-lactamases content of Stenotrophomonas maltophilia strains and to evaluate the virulence potential of these strains with the in vivo Caenorhabditis elegans model. METHODOLOGY: From 1st January 2006 to 31st December 2006, a monitoring programme to study multidrug resistant Gram-negative bacteria including extended-spectrum beta-lactamases (ESBL)-producing S. maltophilia was conducted at Nîmes University Hospital and Perpignan Hospital. The ESBL production was confirmed by the double-disk synergy test using ceftazidime, cefotaxime and cefepime disks associated with clavulanic acid disk. The strains were characterized phenotypically (beta-lactamase[s] identification) and genotypically (pulsed-field gel electrophoresis, plasmid analysis) and evaluated for their virulence with the in vivo nematode C. elegans model (establishment of survival curves [LT50]). RESULTS: Twelve ESBL-producing S. maltophilia strains were isolated in eight patients (median age: 65 years+/-19) mainly during skin infections (41.7%). The ESBL content revealed the presence of four CTX-M-15-producing strains at the same patient. The analysis by ECP confirmed that the four strains were identical. The plasmid analysis demonstrated that the plasmid carrying CTX-M-15 in the worldwide clonal Escherichia coli O25-ST131 strain and S. maltophilia were different. The C. elegans model confirmed that S. maltophilia strains presented a low virulence potential (LT50=4.5days+/-0.5 according to the strains and nematode death in 10days+/-1) whatever their resistance. CONCLUSION: For the first time in France, a CTX-M-15-producing S. maltophilia strain has been identified. The in vivo model confirmed that these bacteria have a low potential virulence. However, these strains were isolated from "immunocompromised" and multihospital patients demonstrating the necessary monitoring of these patients. The CTX-M after diffusing in hospitals and community in E. coli strains seem to spread in other Gram-negative bacteria.