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Background <p>Accurate disease phase assessment remains clinically important in chronic myeloid leukemia (CML), as progression to accelerated or blast phase (AP/BP) is associated with therapeutic resistance and poor prognosis. We aimed to develop an interpretable machine learning (ML) framework integrating peripheral blood long non-coding RNA (lncRNA) expression and clinical variables for disease phase assessment in CML.</p> Methods <p>Using peripheral blood from 305 treatment-naïve CML patients (85 AP/BP; 220 chronic phase) and 90 healthy controls, we identified a progression-associated ten-lncRNA signature via PCR array and real-time quantitative PCR (RT-qPCR) validation. Feature selection using Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariable logistic regression yielded eight key predictors. Five ML models were trained (<i>n</i> = 214), validated in an independent holdout test cohort (<i>n</i> = 91), and evaluated using the area under the ROC curve (AUC), calibration, and decision curve analysis. Interpretability was achieved using SHapley Additive exPlanations (SHAP).</p> Results <p>The final model integrated three lncRNAs (<i>CCDC26</i>, <i>SNHG5</i>, <i>FENDRR</i>) and five clinical variables. Among the evaluated algorithms, XGBoost demonstrated the most favorable overall performance, achieving AUCs of 0.9658 and 0.9656 in the training and independent holdout test cohorts, respectively.</p> Conclusions <p>We developed an interpretable ML framework integrating peripheral blood lncRNAs and clinical variables to support disease phase assessment in CML. The proposed model demonstrated favorable performance within this single-center cohort and may provide complementary information for clinical evaluation. Further multicenter and longitudinal studies are required before broader clinical application.</p>

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An interpretable machine learning model integrating peripheral blood lncRNAs and clinical variables for phase classification in chronic myeloid leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月29日

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  • Yuanyuan Bai,
  • Mengting Zheng,
  • Hongshuang Li,
  • Chenlei Song,
  • Bingxin Huang,
  • Meiyun Cai,
  • Zhanguo Chen

摘要

Background

Accurate disease phase assessment remains clinically important in chronic myeloid leukemia (CML), as progression to accelerated or blast phase (AP/BP) is associated with therapeutic resistance and poor prognosis. We aimed to develop an interpretable machine learning (ML) framework integrating peripheral blood long non-coding RNA (lncRNA) expression and clinical variables for disease phase assessment in CML.

Methods

Using peripheral blood from 305 treatment-naïve CML patients (85 AP/BP; 220 chronic phase) and 90 healthy controls, we identified a progression-associated ten-lncRNA signature via PCR array and real-time quantitative PCR (RT-qPCR) validation. Feature selection using Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariable logistic regression yielded eight key predictors. Five ML models were trained (n = 214), validated in an independent holdout test cohort (n = 91), and evaluated using the area under the ROC curve (AUC), calibration, and decision curve analysis. Interpretability was achieved using SHapley Additive exPlanations (SHAP).

Results

The final model integrated three lncRNAs (CCDC26, SNHG5, FENDRR) and five clinical variables. Among the evaluated algorithms, XGBoost demonstrated the most favorable overall performance, achieving AUCs of 0.9658 and 0.9656 in the training and independent holdout test cohorts, respectively.

Conclusions

We developed an interpretable ML framework integrating peripheral blood lncRNAs and clinical variables to support disease phase assessment in CML. The proposed model demonstrated favorable performance within this single-center cohort and may provide complementary information for clinical evaluation. Further multicenter and longitudinal studies are required before broader clinical application.