RNA-seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature.

Improving outcomes in multiple myeloma will involve not only development of new therapies but also better use of existing treatments. We performed RNA sequencing on samples from newly diagnosed patients enrolled in the phase 2 PADIMAC (Bortezomib, Adriamycin, and Dexamethasone Therapy for Previously Untreated Patients with Multiple Myeloma: Impact of Minimal Residual Disease in Patients with Deferred ASCT) study. Using synthetic annealing and the large margin nearest neighbor algorithm, we developed and trained a 7-gene signature to predict treatment outcome.

Ammonium tetrathiomolybdate following ischemia/reperfusion injury: Chemistry, pharmacology, and impact of a new class of sulfide donor in preclinical injury models.

Background: Early revascularization of ischemic organs is key to improving outcomes, yet consequent reperfusion injury may be harmful. Reperfusion injury is largely attributed to excess mitochondrial production of reactive oxygen species (ROS). Sulfide inhibits mitochondria and reduces ROS production.

Myeloma impairs mature osteoblast function but causes early expansion of osteo-progenitors: temporal changes in bone physiology and gene expression in the KMS12BM model.

Myeloma bone disease results from an uncoupling of osteoclastic resorption and osteoblastic bone formation, but early changes in osteogenic function remain poorly defined. We used the KMS12BM xenograft model to investigate cellular and molecular events at early and late stages of disease. Lytic lesions and changes in osteoblast and osteoclast numbers occur late (8 weeks), however, micro-computed tomography of femora revealed significant reduction in bone volume at earlier disease stages (3 weeks) when tumour burden is low.