Multi-omics differences in the bone marrow between essential thrombocythemia and prefibrotic primary myelofibrosis

Area of Science:

• Hematology
• Oncology
• Genomics and Proteomics

Background:

• Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms.
• These conditions present overlapping clinical features but have significantly different prognoses.
• Current diagnostic methods relying on bone marrow morphology lack sufficient reliability for accurate subtype differentiation.

Purpose of the Study:

• To investigate multi-omics alterations in bone marrow biopsies of patients with ET and pre-PMF.
• To identify differential protein and microbe levels to improve understanding of diagnostic characteristics.
• To discover potential diagnostic biomarkers for ET and pre-PMF.

Main Methods:

• Proteomic analysis using 4D direct data-independent acquisition.
• Microbiome analysis utilizing 2bRAD-M sequencing technology.
• Comparative analysis of laboratory, proteomic, and microbiome data between ET and pre-PMF patient groups.

Main Results:

• Significant differences in lipid metabolism and immune response pathways were observed.
• Pre-PMF showed elevated neutrophil-to-lymphocyte ratio and decreased HDL/cholesterol; ET showed elevated specific proteins (APOC3, APOA4, FABP4, C5, CFB).
• Distinct microbial profiles identified: increased Mycobacterium, Xanthobacter, L1I39 in pre-PMF; decreased Sphingomonas, Brevibacillus, Pseudomonas_E in ET, with high diagnostic accuracy (AUCs 0.786–0.929).

Conclusions:

• Multi-omics profiling reveals distinct proteomic and microbiome signatures in ET and pre-PMF bone marrow.
• Specific proteins (e.g., CXCR2, CXCR4 in pre-PMF; APOC3, APOA4 in ET) and bacterial genera show potential as diagnostic indicators.
• These findings contribute to understanding ET and pre-PMF heterogeneity and may inform improved diagnostic strategies.