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<p>Cytogenetic abnormalities and recurrent gene mutations are central to the biology and prognosis of myelodysplastic syndromes/neoplasms (MDS); however, the significance of patients without detectable genomic lesions remains unclear. In this retrospective analysis of 758 patients with primary MDS, the participants were stratified according to the presence of gene mutations and/or cytogenetic abnormalities. Approximately twenty percent lacked both abnormalities and were characterized by younger age, female predominance, lower IPSS-R/IPSS-M risk, and the most favorable survival outcomes. Bulk RNA sequencing further revealed that mutation-negative/normal-karyotype MDS was characterized by immune-metabolic transcriptional programs, whereas genomically altered disease exhibited inflammatory, proliferative, and stress-response signatures, indicating a biologically distinct low-risk state. Therefore, patients without genomic abnormalities appear to constitute a biologically distinct subgroup of MDS. To refine risk assessment beyond IPSS-M systems, a multivariable Cox-based nomogram was developed incorporating age, ferritin level &gt;800 ng/mL, lactate dehydrogenase level &gt;200 U/L, bone marrow fibrosis, and IPSS-M. The proposed model outperformed IPSS-M alone and remained robust following bootstrap validation, allowing individualized 12- and 36-month survival estimation. These findings underscore the limitations of relying solely on molecular assays for risk stratification and support the integration of clinical, genomic, and model-based predictors to improve classification and guide individualized MDS management.</p>

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Prognostic implications of genetic and transcriptomic abnormalities in MDS according to IPSS-R, IPSS-M, and the International Consensus Classification

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月12日

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  • Wan-Hsuan Lee,
  • Hsin-An Hou,
  • Chien-Chin Lin,
  • Xavier Cheng-Hong Tsai,
  • Feng-Ming Tien,
  • Min-Yen Lo,
  • Yu-Sung Chang,
  • Yen-Ling Peng,
  • Mei-Hsuan Tseng,
  • Yuan-Yeh Kuo,
  • Shan-Chi Yu,
  • Ming-Chih Liu,
  • Chi-Yuan Yao,
  • Chia-Lang Hsu,
  • Chang-Tsu Yuan,
  • Ming Yao,
  • Hwei-Fang Tien,
  • Bor-Sheng Ko,
  • Wen-Chien Chou

摘要

Cytogenetic abnormalities and recurrent gene mutations are central to the biology and prognosis of myelodysplastic syndromes/neoplasms (MDS); however, the significance of patients without detectable genomic lesions remains unclear. In this retrospective analysis of 758 patients with primary MDS, the participants were stratified according to the presence of gene mutations and/or cytogenetic abnormalities. Approximately twenty percent lacked both abnormalities and were characterized by younger age, female predominance, lower IPSS-R/IPSS-M risk, and the most favorable survival outcomes. Bulk RNA sequencing further revealed that mutation-negative/normal-karyotype MDS was characterized by immune-metabolic transcriptional programs, whereas genomically altered disease exhibited inflammatory, proliferative, and stress-response signatures, indicating a biologically distinct low-risk state. Therefore, patients without genomic abnormalities appear to constitute a biologically distinct subgroup of MDS. To refine risk assessment beyond IPSS-M systems, a multivariable Cox-based nomogram was developed incorporating age, ferritin level >800 ng/mL, lactate dehydrogenase level >200 U/L, bone marrow fibrosis, and IPSS-M. The proposed model outperformed IPSS-M alone and remained robust following bootstrap validation, allowing individualized 12- and 36-month survival estimation. These findings underscore the limitations of relying solely on molecular assays for risk stratification and support the integration of clinical, genomic, and model-based predictors to improve classification and guide individualized MDS management.