Biallelic loss of CDKN2A is associated with poor response to treatment in pediatric acute lymphoblastic leukemia. Issue 5 (4th May 2017)

• Record Type: Journal Article
• Authors: Braun, Marcin; Pastorczak, Agata; Fendler, Wojciech; Madzio, Joanna; Tomasik, Bartlomiej; Taha, Joanna; Bielska, Marta; Sedek, Lukasz; Szczepanski, Tomasz; Matysiak, Michal; Derwich, Katarzyna; Lejman, Monika; Kowalczyk, Jerzy; Kazanowska, Bernarda; Badowska, Wanda; Styczynski, Jan; Irga-Jaworska, Nina; Trelinska, Joanna; Zalewska-Szewczyk, Beata; Pierlejewski, Filip; Wlodarska, Iwona; Młynarski, Wojciech
• Is Part Of: Leukemia & lymphoma. Volume 58:Issue 5(2017)
• Page Start: 1162
• Page End: 1171
• Publication Date: 2017-05-04
• Subjects: Childhood BCP-ALL -- microdeletions -- MLPA -- MRD -- 9p21 chromosomal region -- prognostic factors; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2016.1228925
• Languages: English
• ISSNs: 1042-8194

Abstract

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.