Distinct clinical characteristics of DUX4- and PAX5-altered childhood B-lymphoblastic leukemia
Document Type
Article
Publication Date
12-14-2021
Abstract
Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4-and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1 , the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse CIR], 8.9%; 95% confidence interval CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.
Keywords
Minimal residual disease, Poor-prognosis, Risk, Children, Gene, Expression, Adolescents, Subtype, Fusion, DUX4
Divisions
fac_med
Funders
National Medical Research Council, Singapore[NMRC/CSA/0053/2013],National Medical Research Council, Singapore[MOH-000277],Children's Cancer Foundation (Singapore),Singapore Tote Board,Goh Foundation (Singapore),Viva Foundation for Children with Cancer
Publication Title
Blood Advances
Volume
5
Issue
23
Publisher
American Society of Hematology
Publisher Location
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS