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Platelets Outperform Leukocytes in Transcriptomic Liquid Biopsy Profiling of Myeloproliferative Neoplasms
Zhu Shen1, Abhishek Sawalkar2, Jason Wu3
1Department of Biostatistics, Harvard University, Cambridge, MA, USA.
Biorxiv : the Preprint Server for Biology
|April 10, 2026
Summary
Platelet RNA sequencing offers a superior, noninvasive method for monitoring myelofibrosis in myeloproliferative neoplasms (MPNs). This approach detects megakaryocyte dysfunction and fibrogenesis more sensitively than leukocyte-based methods.
Area of Science:
- Hematology
- Molecular Biology
- Genomics
Background:
- Myeloproliferative neoplasms (MPNs) are associated with progressive myelofibrosis, a condition leading to significant morbidity and mortality.
- Current noninvasive methods for monitoring fibrotic progression in MPNs are limited.
- Understanding the molecular mechanisms driving myelofibrosis is crucial for developing effective diagnostic and monitoring strategies.
Purpose of the Study:
- To compare the utility of platelet versus leukocyte transcriptomic profiling for detecting and monitoring myelofibrosis in MPNs.
- To identify specific transcriptomic signatures associated with myelofibrosis in peripheral blood fractions.
- To evaluate the diagnostic performance of platelet-based biomarkers compared to leukocyte-based and clinical models.
Main Methods:
- Comparative RNA sequencing of platelet-enriched and leukocyte-enriched fractions from 76 individuals with MPNs and healthy controls.
- Analysis of differential gene expression, pathway enrichment, and machine learning classification (Multinomial LASSO).
- Validation of platelet transcriptomic signatures for myelofibrosis diagnosis.
Main Results:
- Platelet transcriptomes showed significantly more differential gene expression related to myelofibrosis than leukocyte transcriptomes (3,453 vs. 681 genes).
- Platelet signatures were enriched for proteostasis pathways, indicating megakaryocyte dysfunction, while leukocyte signatures showed immune activation.
- Platelet-based models achieved superior diagnostic performance (AUROC 0.85) for myelofibrosis compared to leukocyte-based (AUROC 0.77) or clinical models (AUROC 0.59).
Conclusions:
- Platelet transcriptomic profiling is a highly sensitive and noninvasive biomarker for monitoring myelofibrosis in MPNs.
- Platelet signatures capture key aspects of megakaryocyte-driven fibrogenesis more effectively than peripheral leukocytes.
- This approach holds promise for improving the clinical management of patients with MPNs.
