August 29, 2022

Blood cancer progression

Vanderbilt researchers used single-cell technologies to explore the accumulation of mutations during blood cancer progression, which could help identify strategies for preventing leukemia before it occurs.

by Leigh MacMillan

Approximately one-third of patients diagnosed with the blood disorder myelodysplastic syndrome (MDS) will progress to secondary acute myeloid leukemia (sAML), a blood cancer. 

P. Brent Ferrell, MD, and colleagues are using single-cell techniques to explore the accumulation of mutations — clonal evolution — during the progression from MDS to sAML. They studied paired MDS and sAML samples from 18 patients who were diagnosed with MDS and progressed to sAML. 

Single-cell genotyping showed patient-specific changes in clonal architecture that occurred in distinct patterns, which the researchers classified as static or dynamic. Single-cell transcriptomic analysis identified gene sets and signaling pathways involved in progression. 

The findings, reported in Blood Cancer Discovery, define serial changes in MDS that have clinical and therapeutic implications. The researchers suggest that analysis of larger data sets could identify specific therapeutic targets, with the hope of identifying strategies for preventing leukemic progression before it occurs.

Other authors of the study included Tiffany Guess, PhD, Chad Potts, Pawan Bhat, Justin Cartailler, Austin Brooks, Clinton Holt, Ashwini Yenamandra, PhD, Ferrin Wheeler, PhD,  Michael Savona, MD, and Jean-Philippe Cartailler, PhD. 

The research was supported by the Vanderbilt-Ingram Cancer Center Ambassadors, National Institutes of Health (grants TR002243, HL138291, CA262287, OH012271), Leukemia & Lymphoma Society, Biff Ruttenberg Foundation, Adventure Alle Fund, Beverly and George Rawlings Research Directorship, and E.P. Evans MDS Foundation.