J. Claire Godbersen

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Chronic lymphocytic leukaemia (CLL) is an accumulative disorder marked by deficient apoptosis. The TP53 homolog TAp63 promotes apoptosis and chemosensitivity in solid tumours and its deregulation may contribute to CLL cell survival. We found that TAp63α was the most prevalent TP63 isoform in CLL. Compared to healthy B cells, TAp63 mRNA was repressed in(More)
Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates(More)
BACKGROUND Stromal-mediated signaling enhances NF-κB pathway activity in chronic lymphocytic leukemia (CLL) B cells, leading to cell survival and chemoresistance. Ubiquitination of IκBα may partially account for constitutive activation of NF-κB. MLN4924 is an investigational agent that inhibits the Nedd8-activating enzyme, thereby neutralizing Cullin-RING(More)
Background: Stromal-mediated signaling enhances NF-kB pathway activity in chronic lymphocytic leukemia (CLL) B cells, leading to cell survival and chemoresistance. Ubiquitination of IkBamay partially account for constitutive activation of NF-kB. MLN4924 is an investigational agent that inhibits the Nedd8activating enzyme, thereby neutralizing Cullin-RING(More)
CDK (cyclin-dependent kinase) inhibitors have shown remarkable activity in CLL, where its efficacy has been linked to inhibition of the transcriptional CDKs (7 and 9) and deregulation of RNA polymerase and short-lived pro-survival proteins such as MCL1. Furthermore, ER (endoplasmic reticulum) stress has been implicated in CDK inhibition in CLL. Here we(More)
Chronic lymphocytic leukemia (CLL) B-cells demonstrate both constitutive and stroma-mediated activation of nuclear factor-κB (NF-κB). NEDD8, a ubiquitin-like protein, regulates activity of Cullin-RING ubiquitin ligases (CRLs) and thus indirectly controls NF-κB activity. Inhibition of CRLs with MLN4924, an investigational agent that targets the(More)
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