In a recent study, researchers identified inflammation-related genes and pathways that appeared associated with leukemic transformation in patients who had myelodysplastic syndrome (MDS) with myelofibrosis (MF). The study results were presented as a letter to the editor in the journal Biomarker Research.

In this retrospective analysis, characteristics of leukemic transformation were compared between patients with the combination of MDS and MF (MDS-MF) vs patients with MDS and not MF. In a patient who had MDS-MF whose MF was of grade 2 to 3 (MF2-3), the researchers examined gene expression levels both prior to and after leukemic transformation, using single-cell sequencing from bone marrow mononuclear cells. Sequencing results for this patient were compared with those of a control individual without MDS and a patient who had acute myeloid leukemia.

In this analysis, a total of 53 patients had MDS-MF, of whom 44 had grade 1 MF (MF1) and 9 had MF2-3. Another 31 patients had MDS without MF. Patients with MDS-MF, with MF1 or MF2-3, and patients with MDS only did not show significant differences in numerous traits. These included age, sex, MDS subtype, International Prognostic Scoring System (IPSS) risk category, or treatment strategy. Poor karyotypes were seen more often with patients who had MDS-MF2-3, compared with MDS only or MDS-MF1. Patients with MDS-MF, even involving MF1 and IPSS low or intermediate-1 risk, showed shorter leukemic transformation times than patients with MDS only did.

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In gene expression analysis, the 20 genes showing the greatest increase in expression with leukemic transformation were acute myeloid leukemia-related genes and inflammation-related genes. The inflammation-related genes showing enhanced expression with leukemic transformation included S100 family genes, RNASE3, and CYBB; the researchers noted that none of these had previously been associated with leukemic transformation in patients with MDS-MF. Multiple ribosomal protein genes showed decreased expression with leukemic transformation.

“In conclusion, this study revealed that MDS-MF with even mild MF had a higher risk of leukemic transformation than MDS without MF, suggesting that MDS-MF should have a different risk classification algorithm and may need special treatment,” the researchers wrote in their report. They also indicated that the S100 family genes, RNASE3, and CYBB may be important to leukemic transformation in MDS-MF.


Hong M, Wu J, Ma L, et al. Inflammation-related genes S100s, RNASE3, and CYBB and risk of leukemic transformation in patients with myelodysplastic syndrome with myelofibrosis. Biomark Res. 2021;9(1):53. doi:10.1186/s40364-021-00304-w