Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia

© The Author(s).Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.This project was supported by the Asociación Española Contra el Cáncer, AECC (project ref.: GC16173697BIGA), by CERCA Program/Generalitat de Catalunya, the Catalan Government: 2014-SGR225 (GRE), Obra Social “La Caixa” and by Celgene Spain. E. Genescà is the recipient of agrant from the Spanish Health Ministry (ISCIII, CA12/00468) and an unrestricted grant from Gilead.A. Gonzalez-Perez is supported by a Ramon y Cajal fellowship (RYC-2013-14554) of the Educational Ministry (Madrid, Spain). This work was also partially supported by FEDER funds from the ISCIII (PT13/0010/0026, CIBERONC (CB16/12/00284 and CB16/12/00400), Madrid, Spain)

Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia

Altres ajuts: This project was supported by the Asociación Española Contra el Cáncer, AECC (project ref.: GC16173697BIGA), Obra Social "La Caixa" and by Celgene Spain. A. Gonzalez-Perez is supported by a Ramon y Cajal fellowship (RYC-2013-14554) of the Educational Ministry (Madrid, Spain). This work was also partially supported by FEDER funds from CIBERONC (CB16/12/00284 and CB16/12/00400), Madrid, Spain).Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation

Research of influence of working conditions on the general incidence of foundrymen

Working conditions of workers in foundries and their influence on morbidity with temporary disability are considered. The results of the distribution of diseases in the foundry shops with different character of production for individual nosological forms. It is noted that the increased levels of noise and vibration, high dust concentration in the air of the working area, significant values of air temperature, the intensity of infrared radiation increase the number of cases of morbidity with temporary disability, such as acute respiratory infections, diseases of the musculoskeletal system, respiratory diseases, infections and skin diseases, etc

Training of engineers on labor protection in technical universities of the Republic of Belarus

The educational-methodical, scientific and research activities of the Department «Labor Protection» of Belarusian Technical University (BNTU) were shown in the article. The disciplines involved in the training of engineers for Industry were briefly covered

A study of working conditions in electroplating shops

The results of the study of working conditions working in electroplating shops. It is shown that the main production factors of working conditions are noise, vibration, dust, gas contamination, relative humidity of air, the severity and intensity of the labor process. The results of the studies have shown that at all workplaces there are exceeding of the permissible values for noise level, the content of harmful substances in the air of the working environment when working directly with the galvanic baths, the relative humidity of the air. It is noted that the work performed on the severity and intensity of the labor process can adversely affect the health of workers

Working conditions in foundries

The factors of the working environment of workplaces determining working conditions of workers in foundries are considered. The excess of permissible levels or concentrations of dust, noise, vibration and other harmful factors in various technological operations of manufacturing castings is resulted

A study of working conditions in foundries when performing welding operations. Foundry production and metallurgy

The results of studies of the factors of the production environment in the workplace in the performance of welding works to eliminate casting defects of castings and measures to protect workers from their impact are researched. It is established that in the workplace of welders there are increased levels of noise in various welding methods, as well as when stripping welds with a hand tool; increased levels of local vibration when working with hand grinders; exceeding the permissible values of the intensity of infrared (thermal) radiation. The results of the study of ultraviolet radiation in various welding operations

DISPERSION OF HARMFUL SUBSTANCES DISCHARGE FROM SOURCES OF FOUNDRY SHOPS IN ENVIRONMEN

The results of dispersion of harmful substances discharge in environment from the sources of casting houses on the enterprise territory, sanitary protection zone and residential community are given