MCW Blood Cancer Scientists Analyze Protein Patterns to Predict Relapse of MDS

Blood Cancer ScientistMyelodysplastic syndromes (MDS) are a group of neoplasms where the bone marrow doesn’t make enough healthy blood cells, which can lead to anemia, infections, and sometimes more dangerous conditions like leukemia. For many patients with MDS, disease relapse remains a significant challenge, even after receiving allogeneic hematopoietic cell transplantation (allo-HCT). A new MCW study offers hope for these patients, showing that proteomic analysis—examining patterns of proteins in the blood—may provide a novel way of predicting relapse after transplantation. Findings from the study, recently published in Biomarker Research, could lead to better monitoring and treatment strategies, and improve outcomes for patients with MDS.

“While genomic models have been used to prognosticate MDS, they haven’t captured all patients at risk of relapse, highlighting the need for additional methods to determine the biological events that predispose people to relapse,” explained Guru Subramanian Guru Murthy, MD, MS, Assistant Professor, Hematology and Oncology, and co-first author of the study. “Given that proteomics analyzes events in the cells that are downstream of the genomic level, we believed it would be able to predict relapse and potentially lead to a multi-omics prediction model.”

“We discovered that certain proteomic signatures and pathways—like hallmark complement and hallmark allograft rejection— were statistically enriched among patients who experienced disease relapse compared to those who did not relapse after transplantation,” he added.

The research team leveraged data from the Center for International Blood and Marrow Transplant Research (CIBMTR) to study 52 patients with MDS who had received allo-HCT; half the patients had relapsed after treatment while the other half had not. Using a test called Slow Off-rate Modified Aptamers (SOMAmer), they examined proteins in the patients’ blood samples and in their DNA to see if there were changes affecting the proteins. While their results showed that under-expression or overexpression of several pathway-level proteins was seen in patients with or without relapse, they discovered that two pathways, hallmark complement, and hallmark allograft rejection, were more active in patients who had a relapse.

“The hallmark complement and hallmark allograft rejection pathways are made up of genes that play roles in the body’s immune system. In patients who had a relapse, certain immune proteins like OLR1, S100A12, GP1BA, and others were higher in levels compared to those who didn’t have a relapse. This suggests that these proteins might be involved in why some patients’ diseases come back after treatment,” explained Dr. Guru Murthy.

While limited studies have evaluated the role of proteomics in MDS, this is the first to examine its association with relapse after allo-HCT. Dr. Guru Murthy said the findings are important for understanding why some patients’ diseases come back after treatment and can help guide future research.

“Our next steps are to validate these findings in a larger cohort of patients, and to develop and validate a multi-omic model that complements genomic models that are currently used in risk stratification and relapse prediction in MDS,” he said.

Read the full study in Biomarker Research.