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Related Experiment Video

Updated: May 28, 2026

Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
06:39

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
PubMed

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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).

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Last Updated: May 28, 2026

Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
06:39

Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome

Published on: October 3, 2018

Constructing and Visualizing Models using Mime-based Machine-learning Framework
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Published on: July 22, 2025

  • 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.