Let's walk through what we found in our new study using single-cell RNA-seq on tumor and immune cells from pts w/ asymptomatic Waldenstrom's Macroglobulinemia - out now in @NatureComms! W/ @Yoshi_konnykid @IrenemGhobrial @gaddyg #wmsm #mmsm 1/.

RT @VincentRK: A historic day for myeloma!! .After 5 decades of research. European Commission / EMA approves Daratumumab as the first eve….

This study was a labor of love! Thanks to all authors, our reviewers who really helped us improve the study, our funders, and of course patients and their families for supporting this research! @LabGhobrial @getz_lab.

Take a look at this commentary by Larry Boise: #mmsm 11/.

There’s a lot more we need to understand… For example, how do we select the right patients for this Tx? We have some clues: the number of copies matters and perhaps the breadth of the gain matters, too. But what about co-occurring abnormalities? 10/.

Why are these results important? MCL1 and PI3K inhibitors are already in clinical trials but show toxicity. The presence of 1q+ enhances sensitivity to these inhibitors, suggesting we could afford to reduce their doses without sacrificing efficacy. #mmsm 9/.

We used scRNA-seq to characterize the drugs’ MoA in 1q+ MM. In contrast to prior reports, we found that MCL1 inhibition caused cell cycle arrest with downregulation of G2M genes and the proteins they encode. This was further enhanced by the combination of MCL1i and PI3Ki. 8/.

We found that whole-arm amplification conferred enhanced sensitivity to MCL1 and PI3K inhibition, suggesting the breadth of the amplification may matter too, in addition to the number of copies! This requires further validation, but helps us think about patient selection. 7/.

If we can’t engineer them, could we perhaps isolate isogenic clones? We tried it in a MM cell line with 1q+. While most clones had 4 copies of chr1q, one clone had 4 copies of the central part of chr1q but 3 copies of the distal part! 6/.

Since we couldn’t engineer isogenic models, we used scRNA-seq to look at a real-life alternative: patient tumors with subclonal 1q+. Subclones with 1q+ showed higher expression levels of MCL1 and the PI3K pathway. #mmsm 5/.

We tried approaching the problem from many angles by combining genetic dependency screens and drug screens. Hat tip to @CancerDepMap @broadinstitute! The results were concordant: 1q+ is associated with enhanced sensitivity to MCL1 and PI3K inhibition! #mmsm 4/.

But how do we target an arm-level gain that impacts a ton of genes? It would help if we could engineer isogenic cell lines with and without 1q+, but this is still technically challenging… Also, most MM cell lines carry 1q+, so there aren’t many controls. 3/.

Gain or amplification of 1q is very frequent in MM and is associated with inferior response to Tx and poor outcomes. Developing targeted therapy for 1q+ MM may thus help many patients who have not benefitted as much from recent advances in MM therapeutics. #mmsm 2/.

Our paper on establishing targeted therapy for patients with myeloma and 1q+ is out in @BloodPortfolio! w/ Liz Lightbody, Mairead Reidy, @gaddyg @IrenemGhobrial and Salomon Manier @DanaFarber @broadinstitute #mmsm. 1/.

RT @NikhilMunshiMD: Major Regulatory Milestone in MM: In response to an application by I2TEAMM and @IMFmyeloma, the European Medicines Agen….

RT @FrancescoMaura4: Happy to share our new work out today on @BloodPortfolio #Blood where we report CD38 loss as recurrent mechanisms of r….

Great step forward for patients with myeloma! IMS/IMWG recommending NGS for the identification of high-risk patients. Also noting many other high-risk genomic/transcriptomic etc. features, that could be incorporated in future iterations as more data becomes available. #mmsm.

RT @FrancescoMaura4: Excited to share our work investigating the mutagenic impact of radiotherapy in hematological cancers out today in @BC….

RT @BenDiamondMD: This was a privilege to work on. Big thanks to all of our co-authors and collaborators for supporting the effort!.

Great timing for this publication, as we discuss the need to improve the identification of patients with SMM at high risk of progression in light of yesterday’s ODAC meeting. Congrats @JbAlberge @ankitkdutta @andreapoletti19 @IrenemGhobrial @gaddyg and team #mmsm.

RT @VJHemOnc: At #IBC2025, we caught up with @RomanosSP (@DanaFarber) to hear the findings from a single-cell sequencing study evaluating t….