Filip Garbicz

Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma Single-cell and spatial multiomics analyses identify breakout lesions as a hotspot for tumor-immune interactions and diversification.

Now out in #Science #Immunology (and also featured on the cover!): Lutz, @simonhaas.bsky.social, Weinhold, & al. use single-cell and spatial multiomics to characterize breakout lesions in #multiplemyeloma, identifying regions of immune and tumor cell coevolution:

Predictors of response to venetoclax and therapeutic potential of CDK7 inhibition in multiple myeloma Key PointsRNA-seq analysis reveals a 6-gene signature that stratifies patients with MM by their predicted response to venetoclax.This study proposes a nove

ashpublications.org/bloodneoplas...

#MyelomaSky

It's my turn to use the FACS

We needed this rain.

Single-cell integration reveals metaplasia in inflammatory gut diseases - Nature The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal a...

www.nature.com/articles/s41...

CD71+ erythroid cells promote multiple myeloma progression and impair anti‐bacterial immune response Multiple myeloma (MM), one of the most frequent haematological malignancies, significantly increases the risk of bacterial infections due to treatment-related side effects, comorbidities and cancer-i....

Thrilled to have contributed to this study on understanding infection susceptibility in myeloma! 🧬 Check it out: onlinelibrary.wiley.com/doi/10.1111/... #Myeloma #Hematology #InfectiousDiseases #Research #mmsm

We hope this work opens new possibilities for targeted therapies in MM. There is a lot of biological validation that needs to be done using these scRNAseq data as a blueprint. More to come! #plasmacell #mmsm

To investigate EndMT features, we tested JQ1, a BET inhibitor known to affect mesenchymal features. However, JQ1 didn’t reverse mesenchymal markers in MM ECs, suggesting that MM ECs may require different, more complex intervention strategies. @JunQiLab

Interestingly, while VEGF inhibitors haven’t shown success in MM, our findings suggest that targeting alternative pathways, such as PDGFA, could disrupt the supportive role of ECs in MM. This needs to be tested in vitro and in vivo before we jump into conclusions!

Fascinatingly, MM ECs are highly interactive within the bone marrow. We found enhanced cell–cell signaling, particularly between ECs and mesenchymal stem cells (MSCs), which likely reinforce MM cell survival and growth.

To dive deeper, we developed a new protocol to isolate & culture ECs from MM patients' bone marrow, allowing us to study these cells’ pro-tumor activities in vitro. This model opens avenues for testing therapies directly on MM-derived ECs!

We observed upregulation of genes like VIM, CTNNB1, and SMAD3 in MM ECs, associated with a shift towards a mesenchymal-like state. This suggests that MM ECs undergo an endothelial-to-mesenchymal transition (EndMT), which may aid MM cell invasion and angiogenesis.

The multiple myeloma microenvironment is defined by an inflammatory stromal cell landscape - Nature Immunology Multiple myeloma disease progression and therapy response are influenced by the bone marrow niche in which the tumor cells reside. To characterize this supportive niche, Cupedo and colleagues use sing...

Madelon's paper: nature.com/articles/s41...
Thanks for the huge help without which this analysis would not be possible!

Using data from @NatImmunol paper by @mdejong.bsky.social et al. we identified unique pathway activations in MM-derived ECs, setting them apart from healthy controls. Key pathways? Epithelial–mesenchymal plasticity (EMP) and TGF-beta. MM microenvironemnt seems very complex #scRNAseq

Characterization and Experimental Use of Multiple Myeloma Bone Marrow Endothelial Cells and Progenitors Multiple myeloma (MM) is a plasma cell malignancy that resides within the bone marrow microenvironment, relying heavily on interactions with its cellular components. Among these, endothelial cells (EC...

Link: mdpi.com/1422-0067/25...
Thread below.

Excited to announce our latest study, where we explored the role of endothelial cells (ECs) and progenitors in #MultipleMyeloma #mmsm (MM) progression! We show how MM bone marrow ECs differ transcriptionally and functionally from those in healthy donors. #hematology #oncology 🧵

Time to start a different kind of conversation.