Greetings, my dear readers,

Today’s newsletter is all about mutations and how they define certain subsets of MDS and CHIP.

The first couple of articles are focused on clonal hematopoiesis of indeterminate potential (CHIP), a precursor for MDS and AML. I enjoyed reading the systemic review and meta-analysis by Singh et al in Blood Advances. One important observation is the low-risk nature of isolated DNMT3A mutations, as described in other CHIP studies. The second CHIP paper addresses the association/causation question between CHIP and cardiovascular disease by showing an unidirectional association between CHIP and atherosclerosis.

The third paper discusses a recurrent clinical situation in patients with MDS and Del5q. Isolated Del5q is usually present in low-risk MDS and defines a subset of patients who respond well to lenalidomide. Some of these patients, however, develop TP53 mutations. As with other studies on TP53 mutations, higher allelic fraction and multi-hit mutations predict worse outcomes.

Next, I included an observation about a specific SF3B1 mutation (E592K variant) with worse outcomes than the typical K700E variant. Interestingly, the E592K variant was not associated with increased ringed sideroblasts, a feature often seen with other SF3B1 variants. The key takeaway is that the specific SF3B1 variant significantly influences how the associated MDS will present and behave.

Finally, if you have a long commute like I do, you might want to listen to my discussion about high-risk MDS on the “HemeOnc Pulse” podcast. Thank you for taking time off your busy schedules to make it to the end of this newsletter!

Best,
Afaf Osman, MD