1. Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia
- Author
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Genescà, Eulàlia, Lazarenkov, Aleksey, Morgades, Mireia., Berbis, G., Ruíz-Xivillé, N., Gómez-Marzo, Paula, Ribera, J., Junca, Jordi, González-Pérez, A., Mercadal, Santiago, Guardia, R., Artola, M. T., Moreno, M. J., Martínez-López, J., Zamora, L., Barba, Pere, Gil, Cristina, Tormo, M., Cladera, Antonia, Novo, Andrés, Pratcorona, M., Nomdedeu, Josep, González-Campos, José, Almeida, M., Cervera, José, Montesinos, Pau, Batlle, Montserrat, Vives Polo, Susana, Esteve Reyner, Jordi, Feliu Frasnedo, Evarist, Sole, F, Orfao, Alberto, Ribera, Jose-Maria, Universitat Autònoma de Barcelona, Asociación Española Contra el Cáncer, Generalitat de Catalunya, Obra Social la Caixa, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Educación (España), European Commission, Fundación 'la Caixa', Government of Catalonia (España), and Fundación La Caixa
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0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,humanos ,Single-nucleotide polymorphism ,Locus (genetics) ,Hematopoietic stem cell transplantation ,Biology ,deleción génica ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,proteína supresora de tumor p14ARF ,lcsh:RC254-282 ,CDKN2B ,03 medical and health sciences ,0302 clinical medicine ,CDKN2A ,hemic and lymphatic diseases ,Tumor Suppressor Protein p14ARF ,medicine ,Humans ,leucemia-linfoma linfoblástico de células T precursoras ,Letter to the Editor ,Molecular Biology ,Cyclin-Dependent Kinase Inhibitor p16 ,Cyclin-Dependent Kinase Inhibitor p15 ,inhibidor p15 de cinasas dependientes de ciclinas ,medicine.diagnostic_test ,lcsh:RC633-647.5 ,Genes, p16 ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Minimal residual disease ,pronóstico ,030104 developmental biology ,MRD ,Genes ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Adult Acute Lymphoblastic Leukemia ,inhibidor p16 de cinasas dependientes de ciclinas ,T-ALL ,Gene Deletion ,CDKN2A/ARF ,Fluorescence in situ hybridization - Abstract
© 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).
- Published
- 2018
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