2016•Leukemia & lymphoma/Leukemia and lymphomaRequires access
Biallelic loss ofCDKN2Ais associated with poor response to treatment in pediatric acute lymphoblastic leukemia
Marcin Braun, Agata Pastorczak, Wojciech Fendler, Joanna Madzio, Bartłomiej Tomasik, Joanna Taha, Marta Bielska, Łukasz Sędek, Tomasz Szczepański, Michał Matysiak, Katarzyna Derwich, Monika Lejman, Jerzy Kowalczyk, Bernarda Kazanowska, Wanda Badowska, Jan Styczyński, Ninela Irga‐Jaworska, Joanna Trelińska, Beata Zalewska‐Szewczyk, Filip Pierlejewski, Iwona Włodarska, Wojciech Młynarski, on behalf of the Polish Pediatric Leukemia/Lymphoma Study Group
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Abstract
The inactivation of tumor suppressor genes located within 9p21 locus (CDKN2A, CDKN2B) occurs in up to 30% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its independent prognostic significance remains controversial. In order to investigate the prognostic impact of deletions and promoter methylation within 9p21, 641 children with newly diagnosed BCP-ALL using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) were investigated. A total of 169 (26.4%) microdeletions in 9p21 were detected, of which 71 were homozygous. Patients with CDKN2A homozygous deletions were older at diagnosis (p < .001), more frequently steroid resistant (p = .049), had higher WBC count (p < .001), higher MRD at Day 15 (p = .013) and lower relapse-free survival [p = .028, hazard ratio: 2.28 (95% confidence interval: 1.09-4.76)] than patients without these alterations. CDKN2A homozygous deletions coexisted with IKZF1 and PAX5 deletions (p < .001). In conclusion, CDKN2A homozygous deletions, but not promoter methylation, are associated with poor response to treatment and increased relapse risk of pediatric BCP-ALL.