Articles Vol. 67 No. CĐ7-Trường ĐH Y Dược Hải Phòng 06/07/2026

CHARACTERIZATION OF THE MUTATIONAL SPECTRUM AND ITS PROGNOSTIC SIGNIFICANCE IN PEDIATRIC ACUTE LEUKEMIA

Bui Thi Huong Giang1,2, Pham Thi Loc1,2
1 Hai Phong University of Medicine and Pharmacy
2 Trường Đại học Y Dược Hải Phòng
DOI: 10.52163/yhc.v67iCD7.5586
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Keywords
Acute leukemia; gene mutation; prognosis; T-ALL; B-ALL; AML.
Abstract

Objective: To determine the frequency of gene mutations and their association with overall survival in pediatric acute leukemia (AL), including T-ALL, B-ALL, and AML.

Materials and Methods: A retrospective secondary analysis of 763 pediatric patients with T-ALL (n=265), B-ALL (n=251), and AML (n=247) was performed using publicly available, de-identified data from St. Jude Cloud (GenomePaint/PeCan). Gene events (SNVs, indels, structural rearrangements, pathogenic fusions) were aggregated. Overall survival was analyzed using Kaplan–Meier and log-rank tests.

Results: High-frequency mutations (>10%) included RUNX1 (46.4%), NRAS (45.9%), NOTCH1 (41.8%), ETV6 (37.9%), KRAS (30.9%), FLT3 (22.0%), MLLT3 (18.2%), WT1 (13.9%), KDM6A (13.0%), BCR (12.6%), TP53 (12.2%), and KIT (11.3%). RUNX1, NRAS, ETV6, and KRAS predominated in B-ALL and AML, whereas NOTCH1 was almost exclusive to T-ALL. Intermediate-frequency mutations (5–10%) included CD56, CBL, EZH2, FOXP1, TPK1, MSH2, MRD5, and KDM4C. NRAS mutation in B-ALL was significantly associated with poorer overall survival (p = 0.005); KRAS mutations showed no significant prognostic impact.

Discussion and Conclusion: The mutational landscape varies markedly across AL subtypes and has potential clinical value for risk stratification and personalized treatment.

References
[1]
Zhou X, Wang J, Patel J, et al. Exploration of coding and non-coding variants in cancer using GenomePaint. Cancer Cell. 2021;39(1):83–95. Google Scholar
[2]
Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–2221. Google Scholar
[3]
Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet. 2013;381(9881):1943–1955. Google Scholar
[4]
Weng AP, Ferrando AA, Lee W, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306(5694):269–271. Google Scholar
[5]
Osato M. Point mutations in the RUNX1/AML1 gene: another paradigm of how hematopoietic transcription factors are altered in leukemia. Int J Hematol. 2004;79(5):380–384. Google Scholar
[6]
Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia adds important prognostic information to cytogenetic risk groups. Blood. 2001;98(6):1752–1759. Google Scholar
[7]
Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–447. Google Scholar
[8]
Ernst T, Chase AJ, Score J, et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet. 2010;42(8):722–726. Google Scholar
[9]
Sanada M, Suzuki T, Shih LY, et al. Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms. Nature. 2009;460(7257):904–908. Google Scholar