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

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 h...

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Autores principales: Genescà, E., Lazarenkov, A., Morgades, M., Berbis, G., Ruíz-Xivillé, N., Gómez-Marzo, P., Ribera, J., Juncà, J., González-Pérez, A., Mercadal, S., Guardia, R., Artola, M. T., Moreno, M. J., Martínez-López, J., Zamora, L., Barba, P., Gil, C., Tormo, M., Cladera, A., Novo, A., Pratcorona, M., Nomdedeu, J., González-Campos, J., Almeida, M., Cervera, J., Montesinos, P., Batlle, M., Vives, S., Esteve, J., Feliu, E., Solé, F., Orfao, A., Ribera, J. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057006/
https://www.ncbi.nlm.nih.gov/pubmed/30041662
http://dx.doi.org/10.1186/s13045-018-0639-8
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author Genescà, E.
Lazarenkov, A.
Morgades, M.
Berbis, G.
Ruíz-Xivillé, N.
Gómez-Marzo, P.
Ribera, J.
Juncà, J.
González-Pérez, A.
Mercadal, S.
Guardia, R.
Artola, M. T.
Moreno, M. J.
Martínez-López, J.
Zamora, L.
Barba, P.
Gil, C.
Tormo, M.
Cladera, A.
Novo, A.
Pratcorona, M.
Nomdedeu, J.
González-Campos, J.
Almeida, M.
Cervera, J.
Montesinos, P.
Batlle, M.
Vives, S.
Esteve, J.
Feliu, E.
Solé, F.
Orfao, A.
Ribera, J. M.
author_facet Genescà, E.
Lazarenkov, A.
Morgades, M.
Berbis, G.
Ruíz-Xivillé, N.
Gómez-Marzo, P.
Ribera, J.
Juncà, J.
González-Pérez, A.
Mercadal, S.
Guardia, R.
Artola, M. T.
Moreno, M. J.
Martínez-López, J.
Zamora, L.
Barba, P.
Gil, C.
Tormo, M.
Cladera, A.
Novo, A.
Pratcorona, M.
Nomdedeu, J.
González-Campos, J.
Almeida, M.
Cervera, J.
Montesinos, P.
Batlle, M.
Vives, S.
Esteve, J.
Feliu, E.
Solé, F.
Orfao, A.
Ribera, J. M.
author_sort Genescà, E.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13045-018-0639-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-60570062018-07-30 Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia Genescà, E. Lazarenkov, A. Morgades, M. Berbis, G. Ruíz-Xivillé, N. Gómez-Marzo, P. Ribera, J. Juncà, J. González-Pérez, A. Mercadal, S. Guardia, R. Artola, M. T. Moreno, M. J. Martínez-López, J. Zamora, L. Barba, P. Gil, C. Tormo, M. Cladera, A. Novo, A. Pratcorona, M. Nomdedeu, J. González-Campos, J. Almeida, M. Cervera, J. Montesinos, P. Batlle, M. Vives, S. Esteve, J. Feliu, E. Solé, F. Orfao, A. Ribera, J. M. J Hematol Oncol Letter to the Editor 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13045-018-0639-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-24 /pmc/articles/PMC6057006/ /pubmed/30041662 http://dx.doi.org/10.1186/s13045-018-0639-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Letter to the Editor
Genescà, E.
Lazarenkov, A.
Morgades, M.
Berbis, G.
Ruíz-Xivillé, N.
Gómez-Marzo, P.
Ribera, J.
Juncà, J.
González-Pérez, A.
Mercadal, S.
Guardia, R.
Artola, M. T.
Moreno, M. J.
Martínez-López, J.
Zamora, L.
Barba, P.
Gil, C.
Tormo, M.
Cladera, A.
Novo, A.
Pratcorona, M.
Nomdedeu, J.
González-Campos, J.
Almeida, M.
Cervera, J.
Montesinos, P.
Batlle, M.
Vives, S.
Esteve, J.
Feliu, E.
Solé, F.
Orfao, A.
Ribera, J. M.
Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia
title Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia
title_full Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia
title_fullStr Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia
title_full_unstemmed Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia
title_short Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia
title_sort frequency and clinical impact of cdkn2a/arf/cdkn2b gene deletions as assessed by in-depth genetic analyses in adult t cell acute lymphoblastic leukemia
topic Letter to the Editor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057006/
https://www.ncbi.nlm.nih.gov/pubmed/30041662
http://dx.doi.org/10.1186/s13045-018-0639-8
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