Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia
Por:
Genesca, E, Lazarenkov, A, Morgades, M, Berbis, G, Ruiz-Xiville, N, Gomez-Marzo, P, Ribera, J, Junca, J, Gonzalez-Perez, A, Mercadal, S, Guardia, R, Artola, MT, Moreno, MJ, Martinez-Lopez, J, Zamora, L, Barba, P, Gil, C, Tormo, M, Cladera, A, Novo, A, Pratcorona, M, Nomdedeu, J, Gonzalez-Campos, J, Almeida, M, Cervera, J, Montesinos, P, Batlle, M, Vives, S, Esteve, J, Feliu, E, Francesc Solé, Orfao, A and Ribera, JM
Publicada:
24 jul 2018
Resumen:
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.
Filiaciones:
:
UAB, Josep Carreras Leukaemia Res Inst IJC, Campus ICO Germans Trias & Pujol, Badalona, Spain
Josep Carreras Leukaemia Res Inst IJC, ALL Res Grp, Cami Escoles S-N,Edifici IJC, Badalona 08916, Spain
:
UAB, Josep Carreras Leukaemia Res Inst IJC, Campus ICO Germans Trias & Pujol, Badalona, Spain
Morgades, M:
UAB, ICO Hosp Germans Trias & Pujol, Clin Hematol Dept, Campus ICO Germans Trias & Pujol, Badalona, Spain
Berbis, G:
UAB, Josep Carreras Leukaemia Res Inst IJC, Campus ICO Germans Trias & Pujol, Badalona, Spain
:
UAB, ICO Hosp Germans Trias & Pujol, Clin Hematol Dept, Campus ICO Germans Trias & Pujol, Badalona, Spain
Gomez-Marzo, P:
UAB, Josep Carreras Leukaemia Res Inst IJC, Campus ICO Germans Trias & Pujol, Badalona, Spain
Ribera, J:
UAB, Josep Carreras Leukaemia Res Inst IJC, Campus ICO Germans Trias & Pujol, Badalona, Spain
UAB, ICO Hosp Germans Trias & Pujol, Clin Hematol Dept, Campus ICO Germans Trias & Pujol, Badalona, Spain
:
UAB, ICO Hosp Germans Trias & Pujol, Clin Hematol Dept, Campus ICO Germans Trias & Pujol, Badalona, Spain
Gonzalez-Perez, A:
Univ Pompeu Fabra, Res Program Biomed Informat, Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Barcelona, Spain
Mercadal, S:
Hosp Duran & Reynals ICO, Clin Hematol Serv, Barcelona, Spain
Guardia, R:
Hosp Josep Trueta ICO, Clin Hematol Serv, Girona, Spain
Artola, MT:
Hosp Univ Donostia, Clin Hematol Serv, Donostia San Sebastian, Spain
Moreno, MJ:
Hosp Virgen Victoria, Clin Hematol Serv, Malaga, Spain
Martinez-Lopez, J:
Univ Complutense, CNIO, Hosp Octubre 12, Hematol Dept, Madrid, Spain
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UAB, ICO Hosp Germans Trias & Pujol, Clin Hematol Dept, Campus ICO Germans Trias & Pujol, Badalona, Spain
Barba, P:
Hosp Univ Vall dHebron, Clin Hematol Serv, Barcelona, Spain
Gil, C:
Hosp Gen Alicante, Clin Hematol Serv, Alicante, Spain
Tormo, M:
Hosp Clin Valencia, Clin Hematol Serv, Valencia, Spain
Cladera, A:
Hosp Son Llatzer, Clin Hematol Serv, Palma De Mallorca, Spain
Novo, A:
Hosp Son Espases, Clin Hematol Serv, Palma De Mallorca, Spain
Pratcorona, M:
Hosp Santa Creu & Sant Pau, Clin Hematol Serv, Barcelona, Spain
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Hosp Santa Creu & Sant Pau, Clin Hematol Serv, Barcelona, Spain
Gonzalez-Campos, J:
Hosp Virgen Rocio, Clin Hematol Serv, Seville, Spain
Almeida, M:
Univ Salamanca, Banco Nacl ADN Carlos III, Salamanca, Spain
Cervera, J:
Inst Invest Sanit La Fe IIS La Fe, Biobanco La Fe, Valencia, Spain
Montesinos, P:
Hosp La Fe, Clin Hematol Serv, Valencia, Spain
:
UAB, ICO Hosp Germans Trias & Pujol, Clin Hematol Dept, Campus ICO Germans Trias & Pujol, Badalona, Spain
:
UAB, ICO Hosp Germans Trias & Pujol, Clin Hematol Dept, Campus ICO Germans Trias & Pujol, Badalona, Spain
Esteve, J:
Hosp Clin Barcelona, Clin Hematol Serv, Barcelona, Spain
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UAB, Josep Carreras Leukaemia Res Inst IJC, Campus ICO Germans Trias & Pujol, Badalona, Spain
Francesc Solé:
UAB, Josep Carreras Leukaemia Res Inst IJC, Campus ICO Germans Trias & Pujol, Badalona, Spain
Orfao, A:
Hosp Clin Univ Salamanca HUS, Inst Biosanit Salamanca IBSAL, CIC, IBMCC CSIC USAL,CIBERONC, Salamanca, Spain
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UAB, ICO Hosp Germans Trias & Pujol, Clin Hematol Dept, Campus ICO Germans Trias & Pujol, Badalona, Spain
Green Published, gold
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