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

Jun Li; Suyu Zong; Yang Wan; Min Ruan; Li Zhang; Wenyu Yang; Xiaojuan Chen; Yao Zou; Yumei Chen; Ye Guo; Peng Wu; Yingchi Zhang; Xiaofan Zhu

doi:10.1097/HS9.0000000000000979

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

Hemasphere. 2023 Nov 22;7(12):e979. doi: 10.1097/HS9.0000000000000979. eCollection 2023 Dec.

Authors

Jun Li^{1

2}, Suyu Zong^{1

2}, Yang Wan^{1

2}, Min Ruan^{1

2}, Li Zhang^{1

2}, Wenyu Yang^{1

2}, Xiaojuan Chen^{1

2}, Yao Zou^{1

2}, Yumei Chen^{1

2}, Ye Guo^{1

2}, Peng Wu^{1

2}, Yingchi Zhang^{1

2}, Xiaofan Zhu^{1

2}

Affiliations

¹ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
² Tianjin Institutes of Health Science, Tianjin, China.

Abstract

Lysine methyltransferase 2A-rearranged acute myeloid leukemia (KMT2A-r AML) is a special entity in the 2022 World Health Organization classification of myeloid neoplasms, characterized by high relapse rate and adverse outcomes. Current risk stratification was established on the treatment response and translocation partner of KMT2A. To study the transcriptomic feature and refine the current stratification of pediatric KMT2A-r AML, we analyzed clinical and RNA sequencing data of 351 patients. By implementing least absolute shrinkage and selection operator algorithm, we identified 7 genes (KIAA1522, SKAP2, EGFL7, GAB2, HEBP1, FAM174B, and STARD8) of which the expression levels were strongly associated with outcomes. We then developed a transcriptome-based score, dividing patients into 2 groups with distinct gene expression patterns and prognosis, which was further validated in an independent cohort and outperformed the LSC17 score. We also found cell cycle, oxidative phosphorylation, and metabolism pathways were upregulated in patients with inferior outcomes. By integrating clinical characteristics, we proposed a simple-to-use prognostic scoring system with excellent discriminability, which allowed us to distinguish allogeneic hematopoietic stem cell transplantation candidates more precisely. In conclusion, pediatric KMT2A-r AML is heterogenous on transcriptomic level and the newly proposed scoring system combining clinical characteristics and transcriptomic features can be instructive in clinical routines.