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

E. Genescà, A. Lazarenkov, M. Morgades, G. Berbis, N. Ruíz-Xivillé, P. Gómez-Marzo, J. Ribera, J. Juncà, A. González-Pérez, S. Mercadal, R. Guardia, M. T. Artola, M. J. Moreno, J. Martínez-López, L. Zamora, P. Barba, C. Gil, M. Tormo, A. Cladera, A. NovoM. Pratcorona, J. Nomdedeu, J. González-Campos, M. Almeida, J. Cervera, P. Montesinos, M. Batlle, S. Vives, J. Esteve, E. Feliu, F. Solé, A. Orfao

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Abstract

© 2018 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.
Original languageEnglish
Article number96
JournalJournal of Hematology and Oncology
Volume11
Issue number1
DOIs
Publication statusPublished - 24 Jul 2018

Keywords

  • CDKN2A/ARF
  • CDKN2B
  • MRD
  • Prognosis
  • T-ALL

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    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., ... Orfao, A. (2018). Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia. Journal of Hematology and Oncology, 11(1), [96]. https://doi.org/10.1186/s13045-018-0639-8