The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL.

Fixed-duration venetoclax-rituximab (VenR) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) in the phase 3 MURANO trial (NCT02005471) resulted in superior progression-free survival (PFS) and overall survival (OS) vs bendamustine-rituximab (BR). We report the final analyses of MURANO (median 7 years follow-up). Patients were randomized to VenR (venetoclax 400 mg daily for 2 years plus monthly rituximab for 6 months; n = 194) or BR (6 months; n = 195).

The mutational landscape and functional effects of noncoding ultraconserved elements in human cancers.

The mutational landscape of phylogenetically ultraconserved elements (UCEs), especially those in noncoding DNAs (ncUCEs), and their functional relevance in cancers remain poorly characterized. Here, we perform a systematic analysis of whole-genome and in-house targeted UCE sequencing datasets from more than 3000 patients with cancer of 13,736 UCEs and demonstrate that ncUCE somatic alterations are common. Using a multiplexed CRISPR knockout screen in colorectal cancer cells, we show that the loss of several altered ncUCEs significantly affects cell proliferation.

Targeting ROR2 homooligomerization disrupts ROR2-dependent signaling and suppresses stem-like cell properties of human breast adenocarcinoma.

Breast cancer stem-like cells (CSCs) are enriched following treatment with chemotherapy, and posited as having a high level of plasticity and enhanced tumor-initiation capacity, which can enable cancer relapse. Here, we show that such features are shared by breast cancer (BCA) cells that express receptor tyrosine kinase-like orphan receptor (ROR2), which is expressed primarily during embryogenesis and by various cancers. We find that Wnt5a can induce ROR2 homooligomerization to activate noncanonical Wnt signaling and enhance tumor-initiation capacity of BCA cells.

Variant Transcript of ROR1 ENST00000545203 Does Not Encode ROR1 Protein.

Drs. John and Ford reported in that a variant transcript encoding receptor tyrosine kinase-like orphan receptor 1 (ROR1), namely ENST00000545203 or variant 3 (), was a predominant transcript of neoplastic or normal cells in the Bioinformatic database, including GTEx and the 33 datasets from TCGA. Unlike the full-length transcript, Drs.

Mutation in Bruton Tyrosine Kinase (BTK) A428D confers resistance To BTK-degrader therapy in chronic lymphocytic leukemia.

Targeting BTK has profoundly changed the face of CLL treatment over the past decade. Iterative advances in the cat and mouse game of resistance and redesign have moved BTK inhibitors from covalent to non-covalent and now targeted protein degraders. However, contrary to the presumption that protein degraders may be impervious to mutations in BTK, we now present clinical evidence that a mutation in the kinase domain of BTK, namely A428D, can confer disease resistance to a BTK degrader currently in clinical trials, that is BGB-16673.