Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling

Cheonghwa Lee, Ha Nui Kim, Jung Ah Kwon, Jinha Hwang, Ji Ye Park, Ok Sarah Shin, Soo Young Yoon, Jung Yoon

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Complex karyotype (CK) is associated with a poor prognosis in both acute myeloid leukemia (AML) and myelodysplastic syndrome with excess blasts (MDS-EB). Transcriptomic analyses have improved our understanding of the disease and risk stratification of myeloid neoplasms; however, CK-specific gene expression signatures have been rarely investigated. In this study, we developed and validated a CK-specific gene expression signature. Differential gene expression analysis between the CK and non-CK groups using data from 348 patients with AML and MDS-EB from four cohorts revealed enrichment of the downregulated genes localized on chromosome 5q or 7q, suggesting that haploinsufficiency due to the deletion of these chromosomes possibly underlies CK pathogenesis. We built a robust transcriptional model for CK prediction using LASSO regression for gene subset selection and validated it using the leave-one-out cross-validation method for fitting the logistic regression model. We established a 10-gene CK signature (CKS) predictive of CK with high predictive accuracy (accuracy 94.22%; AUC 0.977). CKS was significantly associated with shorter overall survival in three independent cohorts, and was comparable to that of previously established risk stratification models for AML. Furthermore, we explored of therapeutic targets among the genes comprising CKS and identified the dysregulated expression of superoxide dismutase 1 (SOD1) gene, which is potentially amenable to SOD1 inhibitors.

Original languageEnglish
Article number5289
Issue number21
Publication statusPublished - 2023 Nov
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 by the authors.


  • AML
  • MDS
  • SOD1
  • complex karyotype
  • gene expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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