Identification of novel myelodysplastic syndromes prognostic subgroups by integration of inflammation, cell-type composition, and immune signatures in the bone marrow

Identification of novel myelodysplastic syndromes prognostic subgroups by integration of inflammation, cell-type composition, and immune signatures in the bone marrow

Blog Article

Mutational profiles of myelodysplastic syndromes (MDS) have read more established that a relatively small number of genetic aberrations, including SF3B1 and SRSF2 spliceosome mutations, lead to specific phenotypes and prognostic subgrouping.We performed a multi-omics factor analysis (MOFA) on two published MDS cohorts of bone marrow mononuclear cells (BMMNCs) and CD34 + cells with three data modalities (clinical, genotype, and transcriptomics).Seven different views, including immune profile, inflammation/aging, retrotransposon (RTE) expression, and cell-type composition, were derived from these modalities to identify the latent factors with significant impact on MDS prognosis.SF3B1 was the only mutation among 13 mutations in the BMMNC cohort, indicating a significant association with high inflammation.This trend was also observed to a lesser extent in the CD34 + cohort.

Interestingly, the MOFA factor representing the inflammation shows a good prognosis for MDS patients with high inflammation.In contrast, SRSF2 mutant cases show a granulocyte-monocyte progenitor (GMP) pattern and high levels of crystal beaded candle holder senescence, immunosenescence, and malignant myeloid cells, consistent with their poor prognosis.Furthermore, MOFA identified RTE expression as a risk factor for MDS.This work elucidates the efficacy of our integrative approach to assess the MDS risk that goes beyond all the scoring systems described thus far for MDS.