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J Hematol Oncol. 2018 Jul 24;11(1):96. doi: 10.1186/s13045-018-0639-8.

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 information

1
Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain. egenesca@carrerasresearch.org.
2
ALL Research Group, Josep Carreras Leukaemia Research Institute (IJC), Camí de les Escoles s/n. Edifici IJC, 08916, Badalona, Spain. egenesca@carrerasresearch.org.
3
Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain.
4
Clinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
5
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain.
6
Clinical Hematology Service, Hospital Duran i Reynals-ICO, Hospitalet del LLobregat, Barcelona, Spain.
7
Clinical Hematology Service, Hospital Josep Trueta-ICO, Girona, Spain.
8
Clinical Hematology Service, Hospital Universitario de Donostia, Donostia, Spain.
9
Clinical Hematology Service, Hospital Vírgen de la Victoria, Málaga, Spain.
10
Hematology Department, Hospital 12 de Octubre, CNIO, Universidad Complutense, Madrid, Spain.
11
Clinical Hematology Service, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.
12
Clinical Hematology Service, Hospital General de Alicante, Alicante, Spain.
13
Clinical Hematology Service, Hospital Clínico de Valencia, Valencia, Spain.
14
Clinical Hematology Service, Hospital Son Llàtzer, Palma, Spain.
15
Clinical Hematology Service, Hospital Son Espases, Palma, Spain.
16
Clinical Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
17
Clinical Hematology Service, Hospital Vírgen del Rocío, Sevilla, Spain.
18
Banco Nacional de ADN Carlos III, Universidad de Salamanca, Salamanca, Spain.
19
Biobanco de la Fe, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain.
20
Clinical Hematology Service, Hospital La Fe, Valencia, Spain.
21
Clinical Hematology Service, Hospital Clínic de Barcelona, Barcelona, Spain.
22
Centro de Investigación del Cáncer (IBMCC-CSIC/USAL) (CIC), Hospital Clínico Universitario de Salamanca (HUS), Instituto Bio-Sanitario de Salamanca (IBSAL), CIBERONC, Salamanca, Spain.

Abstract

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.

KEYWORDS:

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

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