iScience (Feb 2024)

A machine learning model identifies M3-like subtype in AML based on PML/RARα targets

  • Tingting Shao,
  • Jianing Li,
  • Minghai Su,
  • Changbo Yang,
  • Yingying Ma,
  • Chongwen Lv,
  • Wei Wang,
  • Yunjin Xie,
  • Gang Xu,
  • Ce Shi,
  • Xinying Zhou,
  • Huitao Fan,
  • Yongsheng Li,
  • Juan Xu

Journal volume & issue
Vol. 27, no. 2
p. 108947

Abstract

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Summary: The typical genomic feature of acute myeloid leukemia (AML) M3 subtype is the fusion event of PML/RARα, and ATRA/ATO-based combination therapy is current standard treatment regimen for M3 subtype. Here, a machine-learning model based on expressions of PML/RARα targets was developed to identify M3 patients by analyzing 1228 AML patients. Our model exhibited high accuracy. To enable more non-M3 AML patients to potentially benefit from ATRA/ATO therapy, M3-like patients were further identified. We found that M3-like patients had strong GMP features, including the expression patterns of M3 subtype marker genes, the proportion of myeloid progenitor cells, and deconvolution of AML constituent cell populations. M3-like patients exhibited distinct genomic features, low immune activity and better clinical survival. The initiative identification of patients similar to M3 subtype may help to identify more patients that would benefit from ATO/ATRA treatment and deepen our understanding of the molecular mechanism of AML pathogenesis.

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