2024.07.11
REASERCH
Our new paper is out in Leukemia!
Our paper on the biomarker of selinexor (XPO1 inhibitor, FDA approved for R/R MM and DLBCL) sensitivity has been published online in Leukemia (https://rdcu.be/dNofH).
Via CRISPR dropout screens, we found that DDX19 homologue dosage is key for selinexor sensitivity.
Mechanistically, DDX19A/B depletion, but not the loss of either one alone, led to MCL1 mRNA nuclear retention, inducing intrinsic apoptosis. Selinexor treatment and the loss of either DDX19A or DDX19B synergistically induce apoptosis in leukemia cells by reducing MCL1 levels. Importantly, we found a subset of T-ALL lines lowly expressing DDX19B that is significantly sensitive to selinexor-induced cell death.
Next questions are:
• Is there a DDX19B-low T-ALL subset among human T-ALL cases?
• Is DDX19 a new drug target for hematological malignancies?
This work has been primarily done by Tatsuya Terasaki, M.D., Ph.D. candidate.
Congratulations Tatsuya!
Via CRISPR dropout screens, we found that DDX19 homologue dosage is key for selinexor sensitivity.
Mechanistically, DDX19A/B depletion, but not the loss of either one alone, led to MCL1 mRNA nuclear retention, inducing intrinsic apoptosis. Selinexor treatment and the loss of either DDX19A or DDX19B synergistically induce apoptosis in leukemia cells by reducing MCL1 levels. Importantly, we found a subset of T-ALL lines lowly expressing DDX19B that is significantly sensitive to selinexor-induced cell death.
Next questions are:
• Is there a DDX19B-low T-ALL subset among human T-ALL cases?
• Is DDX19 a new drug target for hematological malignancies?
This work has been primarily done by Tatsuya Terasaki, M.D., Ph.D. candidate.
Congratulations Tatsuya!