In MDS, cytogenetic abnormalities are quite common. A particular subtype of MDS known as del(5q) MDS is distinguished by an interstitial deletion of chromosome arm 5q. The drug known as lenalidomide has been approved for patients with MDS but only for patients with del(5q) as patients have shown a statistically significant improvement in terms of alleviating anemia. Lenalidomide is known to be an immunomodulatory drug but its mechanism of action is largely unknown. Therefore, I propose to investigate its mechanism of action in hopes to get a better understanding of this complex disease as well possibly improve treatment of MDS. For that reason, I would like to perform RNA-seq or Whole-Transciptome Shotgun Sequencing with MDS patients vs. patients treated with lenalidomide. From these patients we will collect bone marrow from bone marrow aspirations and isolate hematopoietic stem/progenitor cells by FACS sort using lineage markers. As described earlier, patients treated with lenalidomide will be del(5q) while the control patients will be cytogenetically normal or at least subcategorized based on their cytogenetics.

By examining the differences in mRNA expression, we may get a better understanding into the pathogenesis of MDS as well as insight into how it can be treated.