Age-specific mutation profiles and their prognostic implications in pediatric <i>KMT2A</i>-rearranged acute myeloid leukemia

Driver mutations in KMT2A-rearranged (KMT2A-r) have been identified in acute myeloid leukemia (AML); however, age-related differences in their frequency and prognostic factors remain unclear. In this study, we report age-specific mutation profiles and outcomes in pediatric patients with KMT2A-r AML. In 239 cases of KMT2A-r AML, infants (<1 year, n = 59) showed a significantly higher event-free survival (EFS) and overall survival (OS) compared with children (≥1 year, n = 180). Conversely, in 538 cases of non-KMT2A-r AML, infants exhibited a significantly lower EFS and OS than children. KMT2A::MLLT4 was only detected in children with KMT2A-r AML and was associated with a poor prognosis. In KMT2A-r AML, mutations in signaling pathway genes, such as KRAS, were frequently detected in infants and children. However, the frequency of non-signaling pathway mutations was significantly higher in children. Moreover, non-signaling pathway mutations had no significant effect on the prognosis in infants and children, whereas KRAS mutations were associated with poor prognosis in both groups. Multivariate analysis identified older age, a high white blood cell count, KMT2A::MLLT4, and KRAS mutations as independent adverse prognostic factors for both EFS and OS. These age-specific mutation profiles suggest distinct disease mechanisms across age groups and may help refine risk stratification and treatment strategies for pediatric KMT2A-r AML.

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Publication Details

Journal
Haematologica
Published
2025-10-23
DOI
https://doi.org/10.3324/haematol.2025.288481
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Age-specific mutation profiles and their prognostic implications in pediatric KMT2A-rearranged acute myeloid leukemia

H. Matsuo, Kiminori Terui, Miu Tanaka, Moe Ishikawa et al.
Haematologica
Acute Myeloid Leukemia Research
article

Age-specific mutation profiles and their prognostic implications in pediatric KMT2A-rearranged acute myeloid leukemia

H. Matsuo, Kiminori Terui, Miu Tanaka, Moe Ishikawa, Yuhki Koga, Daisuke Tomizawa, Yuichi Shiraishi, Kenichi Yoshida, Takashi Taga, Norio Shiba, Akio Tawa, Hiroaki Goto, Seishi Ogawa, Kenichi Chiba, Shin‐ichi Tsujimoto, Momoko Nishikori, Genki Yamato, Souichi Adachi, Yasuhito Nannya, Etsuro Ito, Nobutaka Kiyokawa, Ai Okada, Junko Takita, Satoru Miyano, Hiroko Tanaka, Hiroshi Moritake, Yusuke Shiozawa, N. Saito, Kota Shoji, Yasuhide Hayashi, Y Shino, Shinju Iyoda, Michidai Nobe
article en

Abstract

Driver mutations in KMT2A-rearranged (KMT2A-r) have been identified in acute myeloid leukemia (AML); however, age-related differences in their frequency and prognostic factors remain unclear. In this study, we report age-specific mutation profiles and outcomes in pediatric patients with KMT2A-r AML. In 239 cases of KMT2A-r AML, infants (<1 year, n = 59) showed a significantly higher event-free survival (EFS) and overall survival (OS) compared with children (≥1 year, n = 180). Conversely, in 538 cases of non-KMT2A-r AML, infants exhibited a significantly lower EFS and OS than children. KMT2A::MLLT4 was only detected in children with KMT2A-r AML and was associated with a poor prognosis. In KMT2A-r AML, mutations in signaling pathway genes, such as KRAS, were frequently detected in infants and children. However, the frequency of non-signaling pathway mutations was significantly higher in children. Moreover, non-signaling pathway mutations had no significant effect on the prognosis in infants and children, whereas KRAS mutations were associated with poor prognosis in both groups. Multivariate analysis identified older age, a high white blood cell count, KMT2A::MLLT4, and KRAS mutations as independent adverse prognostic factors for both EFS and OS. These age-specific mutation profiles suggest distinct disease mechanisms across age groups and may help refine risk stratification and treatment strategies for pediatric KMT2A-r AML.

Haematologica
University of Miyazaki (JP), Kyushu University (JP), Hirosaki University (JP), Shiga University of Medical Science (JP), Gunma University (JP), Kyoto University (JP), Kyoto Medical Center (JP), Integrated Oncology (United States) (US), Yokohama City University Hospital (JP), Higashiosaka College & Higashiosaka Junior College (JP), Kanagawa Children's Medical Center (JP), National Center For Child Health and Development (JP), National Hospital Organization (JP), Gunma Children's Medical Center (JP), Kyoto University Hospital (JP), Children's Cancer Center (US), Nagoya Medical Center (JP), Shiga Medical Center (JP), National Cancer Research Institute (GB), The University of Tokyo (JP), Nippon Medical School (JP), Yokohama City University (JP), Kindai University (JP)
Japan Society for the Promotion of Science, Institute of Medical Science, University of Tokyo
Openalex Percentile: Top 62%
Acute Myeloid Leukemia Research
DOIOpen Access PDFOpenAlex
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