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Updated: May 28, 2026
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Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
Prognostic Score for Myelodysplastic Syndromes Based on Molecular Evolution.
Ivan Civettini1,2,3, Federica Malighetti1, Matteo Villa1
1Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
NEJM Evidence
|May 26, 2026
Summary
This study introduces ProgEvo, a framework that analyzes molecular evolution in myelodysplastic syndromes to improve patient risk stratification. The resulting IPSS-M-Evo model enhances prognostic accuracy by integrating evolutionary insights with clinical data.
Area of Science:
- Hematology
- Genomics
- Computational Biology
Background:
- Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders with variable leukemic transformation risk.
- Accurate prognostic stratification is crucial for MDS clinical decision-making due to significant heterogeneity.
- Existing models may not fully capture the dynamic molecular evolution underlying MDS progression.
Purpose of the Study:
- To develop and validate ProgEvo, a novel framework for inferring molecular evolutionary trajectories in MDS.
- To integrate these evolutionary insights with clinical data to enhance prognostic accuracy.
- To create an improved risk stratification model for MDS patients.
Main Methods:
- ProgEvo was trained on a large cohort (2519 patients) and validated on two independent external cohorts (Genomed4All and Moffitt Cancer Center).
- Directional evolutionary routes were identified and selected based on their association with leukemia-free survival.
- Evolution-informed variables were integrated into the existing IPSS-M model using a multivariable feature selection strategy.
Main Results:
- ProgEvo identified 1765 gene co-occurrences forming 45 directional evolutionary routes, with 18 validated.
- The integrated IPSS-M-Evo model incorporated five evolution-informed variables, including specific gene routes (ASXL1→KRAS, SRSF2→NRAS) and early mutations (ATRX, JAK2).
- IPSS-M-Evo demonstrated improved discrimination for leukemia-free and overall survival, reclassifying over 40% of patients in the Genomed4All cohort.
Conclusions:
- ProgEvo successfully inferred a molecular evolution model and enabled the development of the IPSS-M-Evo prognostic tool.
- The IPSS-M-Evo model offers enhanced prognostic accuracy for MDS by integrating molecular evolution.
- Free web-based tools are available for clinicians to calculate IPSS-M-Evo scores and explore evolutionary trajectories.
