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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Detalles Bibliográficos
Autores: Genesca, E., Lazarenkov, A., Morgades, Mireia, Berbis, G., Ruiz-Xiville, N., Gomez-Marzo, P., Ribera, J., Junca, J., Gonzalez-Perez, A., Mercadal, S., Guardia, R., Artola, M. T., Moreno, M. J., Martinez-Lopez, J., Zamora, Lurdes, Barba, Pere, Gil, C., Tormo, Mar, Cladera-Serra, Antonia, Novo, Andrés, Pratcorona, M., Nomdedeu, J., Gonzalez-Campos, J., Almeida, M., Cervera, Jose, Montesinos, P., Batlle, Montse, Vives, Susana, Esteve, Jordi, Feliu, Evarist, Sole, Francesc, Orfao, A., Ribera, Josep-Maria
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/9207
Acceso en línea:https://hdl.handle.net/20.500.13003/9207
Access Level:acceso abierto
Palabra clave:Prognosis
Gene Deletion
Tumor Suppressor Protein p14ARF
Humans
Cyclin-Dependent Kinase Inhibitor p15
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Genes, p16
Cyclin-Dependent Kinase Inhibitor p16
Genes p16
Inhibidor p16 de la Quinasa Dependiente de Ciclina
Leucemia-Linfoma Linfoblástico de Células T Precursoras
Proteína p14ARF Supresora de Tumor
Humanos
Pronóstico
Inhibidor p15 de las Quinasas Dependientes de la Ciclina
Eliminación de Gen
T-ALL
CDKN2A/ARF
CDKN2B
MRD
Descripción
Sumario: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.

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