Kudos to my first trainees: Sofia, Saurav, and the whole team of the Glytsou Lab.

Huge thanks to my mentors and all our collaborators throughout this journey.

We also thank the editors and reviewers.

Our studies that shed light on developing more effective leukemia therapies would not have been possible without support from the NIH, @bloodcancerunited.bsky.social
, Rutgers Cancer Institute, the V Foundation, and the NJCCR.

Extensive metabolomics, fluxomics & transcriptomics revealed that OPA1 inhibition rewires AML metabolism, rendering AML cells dependent on glutamine, sensitive to glutamine depletion/glutaminase inhibition, & prone to erastin-induced lipid peroxidation/ferroptosis.

Mechanistically, OPA1 inhibitors amplify apoptotic cristae remodeling upon stimulation and sensitize AML models to programmed cell death, independent of the mutational background.

We next leveraged the first-in-class small molecules that inhibit OPA1, developed by the team of Luca Scorrano
pubmed.ncbi.nlm.nih.gov/40614185/ and showed that they synergize with BH3-mimetic drugs to curtail resistance in AML PDXs in vivo, without affecting healthy hematopoietic cells.

Genetic targeting of OPA1 in combination with venetoclax significantly extends animal survival in AML xenograft models.

Using electron microscopy and morphometric analyses in AML cell lines and patient samples, we demonstrate that OPA1-dependent tightening of mitochondrial cristae is a common feature of therapy-resistant AML.

We'll cover 4 key areas:
• Epigenetic & chromatin mechanisms
• Post-transcriptional regulation
• Translational/post-translational control
• Metabolism & mitochondrial biology
www.hematology.org/meetings/ann...