Mutational Landscape and Clinical Outcome of Pediatric Acute Myeloid Leukemia with 11q23/KMT2A Rearrangements

Overview

Journal Cancer Med

Specialty Oncology

Date 2022 Jul 14

PMID 35833755

Authors

Ka-Yuk Yuen

Yong Liu

Yong-Zhuo Zhou

Yin Wang

Dun-Hua Zhou

Jian-Pei Fang

Lu-Hong Xu

Affiliations

Soon will be listed here.

Abstract

Background: Alterations of 11q23/KMT2A are the most prevalent cytogenetic abnormalities in acute myeloid leukemia (AML) and the prognostic significance of 11q23/KMT2A-rearranged AML based on various translocation partners varies among different studies. However, few studies evaluated the molecular characteristics of 11q23/KMT2A-rearranged pediatric AML. We aim to analyze the mutational landscape of 11q23/KMT2A-rearranged AML and assess their prognostic value in outcomes.

Methods: The mutational landscape and clinical prognosis of 105 children with 11q23/KMT2A-rearranged AML in comparison with 277 children with non-11q23/KMT2A-rearranged AML were analyzed using publicly accessible next-generation sequencing data from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset.

Results: Pediatric AML patients with 11q23/KMT2A-rearrangements harbored a low number of mutations (Median, 1 mutation/patient, range, 1-22), 58% of which involved in RAS pathway mutations (KRAS, NRAS, and PTPN11) and 10.5% of which comprised of SETD2 mutations. Compared with non-11q23/KMT2A-rearranged AML, the incidence of KRAS (32.4% vs. 10.1%, P〈0.001) and SETD2 (10.5% vs. 1.4%, P=0.001) gene mutations in 11q23/KMT2A-rearranged AML was significantly higher. Both KRAS and SETD2 mutations occurred more often in t(10;11)(p12;q23). KRAS mutations were correlated with worse 5-year event-free survival [EFS] (Plog-rank = 0.001) and 5-year overall survival [OS] (Plog-rank = 0.009) and the presence of SETD2 mutations increases the 5-year relapse rate (PGray = 0.004). Multivariate analyses confirmed KRAS mutations in 11q23/KMT2A-rearranged AML as an independent predictor for poor EFS (hazard ratio [HR] = 2.10, P=0.05) and OS (HR = 2.39, P=0.054).

Conclusion: Our findings show that pediatric patients with 11q23/KMT2A rearrangements have characteristic mutation patterns and varying clinical outcomes depending on different translocation partners, which could be utilized to develop more accurate risk stratification and tailored therapies.

Citing Articles

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Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring Rearrangement and Its Prognostic Factors.

Jiang B, Zhao Y, Luo Y, Yu J, Chen Y, Ye B Cell Transplant. 2024; 33:9636897231225821.

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Integration of Transcriptomic Features to Improve Prognosis Prediction of Pediatric Acute Myeloid Leukemia With KMT2A Rearrangement.

Li J, Zong S, Wan Y, Ruan M, Zhang L, Yang W Hemasphere. 2023; 7(12):e979.

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Advances in molecular characterization of pediatric acute megakaryoblastic leukemia not associated with Down syndrome; impact on therapy development.

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Mutational landscape and clinical outcome of pediatric acute myeloid leukemia with 11q23/KMT2A rearrangements.

Yuen K, Liu Y, Zhou Y, Wang Y, Zhou D, Fang J Cancer Med. 2022; 12(2):1418-1430.

PMID: 35833755 PMC: 9883550. DOI: 10.1002/cam4.5026.

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