Distinct clinical characteristics of DUX4- and PAX5-altered childhood B-lymphoblastic leukemia

Li, Zhenhua and Lee, Shawn Hsien Ren and Chin, Winnie Hui Ni and Lu, Yi and Jiang, Nan and Lim, Evelyn Huizi and Coustan-Smith, Elaine and Chiew, Kean Hui and Oh, Bernice Ling Zhi and Koh, Grace Shimin and Chen, Zhiwei and Kham, Shirley Kow Yin and Quah, Thuan Chong and Lin, Hai Peng and Tan, Ah Moy and Ariffin, Hany and Yang, Jun J. and Yeoh, Allen Eng-Juh (2021) Distinct clinical characteristics of DUX4- and PAX5-altered childhood B-lymphoblastic leukemia. Blood Advances, 5 (23). pp. 5226-5238. ISSN 2473-9529, DOI https://doi.org/10.1182/bloodadvances.2021004895..

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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.

Item Type: Article
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
Uncontrolled Keywords: Minimal residual disease;Poor-prognosis;Risk;Children;Gene;Expression;Adolescents;Subtype;Fusion;DUX4
Subjects: R Medicine
R Medicine > RC Internal medicine
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 31 May 2022 07:25
Last Modified: 31 May 2022 07:25
URI: http://eprints.um.edu.my/id/eprint/34630

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