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

被引：21

作者：

Genesca, E. ^{[1
,21
]}

Lazarenkov, A. ^{[1
]}

Morgades, M. ^{[2
]}

Berbis, G. ^{[1
]}

Ruiz-Xiville, N. ^{[2
]}

Gomez-Marzo, P. ^{[1
]}

Ribera, J. ^{[1
]}

Junca, J. ^{[2
]}

Gonzalez-Perez, A. ^{[3
]}

Mercadal, S. ^{[4
]}

Guardia, R. ^{[5
]}

Artola, M. T. ^{[6
]}

Moreno, M. J. ^{[7
]}

Martinez-Lopez, J. ^{[8
]}

Zamora, L. ^{[2
]}

Barba, P. ^{[9
]}

Gil, C. ^{[10
]}

Tormo, M. ^{[11
]}

Cladera, A. ^{[12
]}

Novo, A. ^{[13
]}

Pratcorona, M. ^{[14
]}

Nomdedeu, J. ^{[14
]}

Gonzalez-Campos, J. ^{[15
]}

Almeida, M. ^{[16
]}

Cervera, J. ^{[17
]}

Montesinos, P. ^{[18
]}

Batlle, M. ^{[2
]}

Vives, S. ^{[2
]}

Esteve, J. ^{[19
]}

Feliu, E. ^{[1
]}

Sole, F. ^{[1
]}

Orfao, A. ^{[20
]}

Ribera, J. M. ^{[2
]}

机构：

[1] UAB, Josep Carreras Leukaemia Res Inst IJC, Campus ICO Germans Trias & Pujol, Badalona, Spain

[2] UAB, ICO Hosp Germans Trias & Pujol, Clin Hematol Dept, Campus ICO Germans Trias & Pujol, Badalona, Spain

[3] Univ Pompeu Fabra, Res Program Biomed Informat, Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Barcelona, Spain

[4] Hosp Duran & Reynals ICO, Clin Hematol Serv, Barcelona, Spain

[5] Hosp Josep Trueta ICO, Clin Hematol Serv, Girona, Spain

[6] Hosp Univ Donostia, Clin Hematol Serv, Donostia San Sebastian, Spain

[7] Hosp Virgen Victoria, Clin Hematol Serv, Malaga, Spain

[8] Univ Complutense, CNIO, Hosp Octubre 12, Hematol Dept, Madrid, Spain

[9] Hosp Univ Vall dHebron, Clin Hematol Serv, Barcelona, Spain

[10] Hosp Gen Alicante, Clin Hematol Serv, Alicante, Spain

[11] Hosp Clin Valencia, Clin Hematol Serv, Valencia, Spain

[12] Hosp Son Llatzer, Clin Hematol Serv, Palma De Mallorca, Spain

[13] Hosp Son Espases, Clin Hematol Serv, Palma De Mallorca, Spain

[14] Hosp Santa Creu & Sant Pau, Clin Hematol Serv, Barcelona, Spain

[15] Hosp Virgen Rocio, Clin Hematol Serv, Seville, Spain

[16] Univ Salamanca, Banco Nacl ADN Carlos III, Salamanca, Spain

[17] Inst Invest Sanit La Fe IIS La Fe, Biobanco La Fe, Valencia, Spain

[18] Hosp La Fe, Clin Hematol Serv, Valencia, Spain

[19] Hosp Clin Barcelona, Clin Hematol Serv, Barcelona, Spain

[20] Hosp Clin Univ Salamanca HUS, Inst Biosanit Salamanca IBSAL, CIC, IBMCC CSIC USAL,CIBERONC, Salamanca, Spain

[21] Josep Carreras Leukaemia Res Inst IJC, ALL Res Grp, Cami Escoles S-N,Edifici IJC, Badalona 08916, Spain

来源：

JOURNAL OF HEMATOLOGY & ONCOLOGY | 2018年 / 11卷

关键词：

T-ALL; CDKN2A/ARF; CDKN2B; Prognosis; MRD; MINIMAL RESIDUAL DISEASE;

D O I：

10.1186/s13045-018-0639-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：4

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