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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:227971 |
| Acceso en línea: | https://ddd.uab.cat/record/227971 https://dx.doi.org/urn:doi:10.1186/s13045-018-0639-8 |
| Access Level: | acceso abierto |
| Palabra clave: | T-ALL CDKN2A/ARF CDKN2B Prognosis MRD |
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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 leukemiaGenescà, Eulàlia|||0000-0002-5657-4842Lazarenkov, Aleksey|||0000-0003-0652-8116Morgades, Mireia|||0000-0003-0295-2534Berbis, G.Ruíz-Xivillé, NeusGómez-Marzo, Paula|||0000-0002-6829-9630Ribera, Jose-Maria|||0000-0003-1042-6024Junca, Jordi|||0000-0003-0142-772XGonzalez-Perez, Abel|||0000-0002-8582-4660Mercadal, Santiago|||0000-0003-4741-7885Guàrdia, RamónArtola, Maria TeresaMoreno, Maria JoséMartínez-López, Joaquín F.Zamora, Lurdes|||0000-0003-1713-7110Barba, Pere|||0000-0001-7076-7969Gil, CristinaTormo, Mar|||0000-0001-9622-1649Cladera, AntoniaNovo, AndrésPratcorona, Marta|||0000-0001-6375-596XNomdedeu Guinot, Jose Francisco|||0000-0003-3399-346XGonzález Campos, JoséAlmeida Parra, MaríaCervera, José|||0000-0001-8252-1106Montesinos, Pau|||0000-0002-3275-5593Batlle, Montserrat|||0000-0002-3034-2023Vives Polo, Susana|||0000-0003-2217-5285Esteve Reyner, Jordi|||0000-0002-8056-648XFeliu Frasnedo, Evarist|||0000-0001-5780-3136Sole, F.|||0000-0002-3251-2161Orfao, Alberto|||0000-0002-0007-7230Ribera, Jose-Maria|||0000-0003-1042-6024T-ALLCDKN2A/ARFCDKN2BPrognosisMRDRecurrent 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.Universitat Autònoma de Barcelona 22018-01-0120182018-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/227971https://dx.doi.org/urn:doi:10.1186/s13045-018-0639-8reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-225Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PT13-0010-0026Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CA12-00468open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2279712026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
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 |
| spellingShingle |
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, Eulàlia|||0000-0002-5657-4842 T-ALL CDKN2A/ARF CDKN2B Prognosis MRD |
| 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_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_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 |
| dc.creator.none.fl_str_mv |
Genescà, Eulàlia|||0000-0002-5657-4842 Lazarenkov, Aleksey|||0000-0003-0652-8116 Morgades, Mireia|||0000-0003-0295-2534 Berbis, G. Ruíz-Xivillé, Neus Gómez-Marzo, Paula|||0000-0002-6829-9630 Ribera, Jose-Maria|||0000-0003-1042-6024 Junca, Jordi|||0000-0003-0142-772X Gonzalez-Perez, Abel|||0000-0002-8582-4660 Mercadal, Santiago|||0000-0003-4741-7885 Guàrdia, Ramón Artola, Maria Teresa Moreno, Maria José Martínez-López, Joaquín F. Zamora, Lurdes|||0000-0003-1713-7110 Barba, Pere|||0000-0001-7076-7969 Gil, Cristina Tormo, Mar|||0000-0001-9622-1649 Cladera, Antonia Novo, Andrés Pratcorona, Marta|||0000-0001-6375-596X Nomdedeu Guinot, Jose Francisco|||0000-0003-3399-346X González Campos, José Almeida Parra, María Cervera, José|||0000-0001-8252-1106 Montesinos, Pau|||0000-0002-3275-5593 Batlle, Montserrat|||0000-0002-3034-2023 Vives Polo, Susana|||0000-0003-2217-5285 Esteve Reyner, Jordi|||0000-0002-8056-648X Feliu Frasnedo, Evarist|||0000-0001-5780-3136 Sole, F.|||0000-0002-3251-2161 Orfao, Alberto|||0000-0002-0007-7230 Ribera, Jose-Maria|||0000-0003-1042-6024 |
| author |
Genescà, Eulàlia|||0000-0002-5657-4842 |
| author_facet |
Genescà, Eulàlia|||0000-0002-5657-4842 Lazarenkov, Aleksey|||0000-0003-0652-8116 Morgades, Mireia|||0000-0003-0295-2534 Berbis, G. Ruíz-Xivillé, Neus Gómez-Marzo, Paula|||0000-0002-6829-9630 Ribera, Jose-Maria|||0000-0003-1042-6024 Junca, Jordi|||0000-0003-0142-772X Gonzalez-Perez, Abel|||0000-0002-8582-4660 Mercadal, Santiago|||0000-0003-4741-7885 Guàrdia, Ramón Artola, Maria Teresa Moreno, Maria José Martínez-López, Joaquín F. Zamora, Lurdes|||0000-0003-1713-7110 Barba, Pere|||0000-0001-7076-7969 Gil, Cristina Tormo, Mar|||0000-0001-9622-1649 Cladera, Antonia Novo, Andrés Pratcorona, Marta|||0000-0001-6375-596X Nomdedeu Guinot, Jose Francisco|||0000-0003-3399-346X González Campos, José Almeida Parra, María Cervera, José|||0000-0001-8252-1106 Montesinos, Pau|||0000-0002-3275-5593 Batlle, Montserrat|||0000-0002-3034-2023 Vives Polo, Susana|||0000-0003-2217-5285 Esteve Reyner, Jordi|||0000-0002-8056-648X Feliu Frasnedo, Evarist|||0000-0001-5780-3136 Sole, F.|||0000-0002-3251-2161 Orfao, Alberto|||0000-0002-0007-7230 |
| author_role |
author |
| author2 |
Lazarenkov, Aleksey|||0000-0003-0652-8116 Morgades, Mireia|||0000-0003-0295-2534 Berbis, G. Ruíz-Xivillé, Neus Gómez-Marzo, Paula|||0000-0002-6829-9630 Ribera, Jose-Maria|||0000-0003-1042-6024 Junca, Jordi|||0000-0003-0142-772X Gonzalez-Perez, Abel|||0000-0002-8582-4660 Mercadal, Santiago|||0000-0003-4741-7885 Guàrdia, Ramón Artola, Maria Teresa Moreno, Maria José Martínez-López, Joaquín F. Zamora, Lurdes|||0000-0003-1713-7110 Barba, Pere|||0000-0001-7076-7969 Gil, Cristina Tormo, Mar|||0000-0001-9622-1649 Cladera, Antonia Novo, Andrés Pratcorona, Marta|||0000-0001-6375-596X Nomdedeu Guinot, Jose Francisco|||0000-0003-3399-346X González Campos, José Almeida Parra, María Cervera, José|||0000-0001-8252-1106 Montesinos, Pau|||0000-0002-3275-5593 Batlle, Montserrat|||0000-0002-3034-2023 Vives Polo, Susana|||0000-0003-2217-5285 Esteve Reyner, Jordi|||0000-0002-8056-648X Feliu Frasnedo, Evarist|||0000-0001-5780-3136 Sole, F.|||0000-0002-3251-2161 Orfao, Alberto|||0000-0002-0007-7230 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
T-ALL CDKN2A/ARF CDKN2B Prognosis MRD |
| topic |
T-ALL CDKN2A/ARF CDKN2B Prognosis MRD |
| 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. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2 2018-01-01 2018 2018-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/227971 https://dx.doi.org/urn:doi:10.1186/s13045-018-0639-8 |
| url |
https://ddd.uab.cat/record/227971 https://dx.doi.org/urn:doi:10.1186/s13045-018-0639-8 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-225 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PT13-0010-0026 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CA12-00468 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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