A5003613067- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Myeloproliferative Neoplasms: Diagnosis and Treatment
Brigham and Women's Hospital
2022
There is a growing body of evidence that therapy-related myeloid neoplasms (t-MNs) with driver gene mutations arise in the background clonal hematopoiesis (CH) under positive selective pressure chemo- and radiation therapies. Uncovering exposure relationships provide advantage to specific CH critical understanding pathogenesis etiology t-MNs. In systematic analysis 416 patients t-MN detailed prior history, we found TP53 were significantly associated treatment thalidomide analogs,...
Targeted protein degradation is a rapidly advancing and expanding therapeutic approach. Drugs that degrade GSPT1 via the CRL4CRBN ubiquitin ligase are new class of cancer therapy in active clinical development with evidence activity against acute myeloid leukemia early-phase trials. However, other than activation integrated stress response, downstream effects leading to cell death largely undefined, no murine models available study these agents. We identified domains essential for survival...