Non-invasive detection of bone marrow fibrosis in myeloproliferative neoplasms using cell-free RNA

Area of Science:

• Hematology
• Molecular Biology
• Oncology

Background:

• Myeloproliferative neoplasms (MPNs) are blood cancers characterized by abnormal cell growth.
• Myelofibrosis (MF) is a serious complication of MPNs, involving bone marrow fibrosis and disrupted blood cell production.
• Current detection of bone marrow fibrosis relies on invasive biopsy procedures.

Purpose of the Study:

• To investigate if cell-free RNA (cf-RNA) transcriptomic profiling in peripheral blood can detect bone marrow fibrosis in MPN patients.
• To identify specific molecular pathways and biomarkers associated with different grades of myelofibrosis.

Main Methods:

• Transcriptomic profiling of cf-RNA from peripheral blood of MPN patients with JAK2V617F mutation.
• Correlation analysis of gene expression patterns with reticulin fibrosis grades assessed by bone marrow biopsy.
• Analysis of key transcription factors (e.g., RUNX1) and inflammatory mediators (e.g., IL-18).
• Functional assays to confirm the role of identified mediators in fibrotic processes.

Main Results:

• Significant gene expression changes in cf-RNA correlated with reticulin fibrosis grades.
• Advanced fibrosis (grades 2-3) showed upregulated TGF-β pathways and extracellular matrix remodeling markers.
• Grade 3 fibrosis was linked to increased proliferation signals and inflammatory markers (S100A8/9).
• RUNX1 was identified as a key transcription factor promoting myofibroblast differentiation.
• Elevated IL-18 plasma levels correlated with high-grade fibrosis and induced fibrotic transformation in mesenchymal stromal cells.

Conclusions:

• cf-RNA transcriptomics can detect bone marrow fibrosis in MPN patients.
• TGF-β, ECM remodeling, RUNX1, and IL-18 are key players in MPN-associated fibrosis.
• IL-18 is a promising biomarker for high-grade fibrosis and a potential therapeutic target.