PAX5 overexpression

Overexpression of PAX5 resulted in increased CCND1 expression. These results support the importance of rs9344 G enhancer in increasing CCND1 expression in MM.

Moreover, Brevilin A delayed tumor formation in vivo. Brevilin A inhibited PCa progression by regulating SOX4 expression in a PAX5-dependent manner, providing a promising anti-tumor drug for PCa.

Furthermore, the in vitro and in vivo experiments revealed that NPC tissue and cell lines had low mRNA expression levels of PAX5, the PAX5 promoter was hypermethylated in NPC cell lines, and PAX5 overexpression inhibited NPC cell proliferation and tumor growth in nude mice. PAX5 may be a tumor suppressor and serve as a novel potential diagnostic and prognostic marker for NPC.

P1/2, N=23, Suspended, City of Hope Medical Center | Trial completion date: Dec 2023 --> Nov 2024 | Recruiting --> Suspended | Trial primary completion date: Dec 2023 --> Nov 2024

These results indicate the relapse-enriched gene expression signature can effectively risk-stratify newly diagnosed pediatric AML patients. Ongoing studies are focused on validating this signature in other independent cohorts, as well as integrating it with cytogenetic features and other previously reported signatures of relevance such as LSC to establish its prognostic utility.

P3, N=352, Active, not recruiting, Pharmacyclics LLC. | Trial completion date: Sep 2023 --> Nov 2024 | Trial primary completion date: Sep 2023 --> Nov 2024

Bortezomib and dexamethasone therapy was initiated, but the patient succumbed to the disease on the 8th day of hospitalization. Similar to our present case, PCL cases with "lymphocytosis" have been widely reported, which some speculating the involvement of PAX5 overexpression in the pathogenesis. Such cases, including ours, may be classified as a unique group of disorders (PCL presenting as "lymphocytosis"), which requires accurate differential diagnosis and subsequent urgent multidisciplinary intensive treatment.

Performing an ex-vivo drug screening with 174 drugs in early to late clinical trials on blasts of 3 IKZF1plus DS-ALL patients and on 14 controls (5 B-cell lymphoblastoid cell lines, 3 PBMCs, 3 T-cells and 3 CD34+ cells, all derived from healthy donors) we observed the efficacy of drugs known to be effective in Ph-like patients such as Birinapant, a SMAC mimetic, and HDAC inhibitors...Ph-like signature and IKZF1 deletions were associated with poor outcome, with the risk of relapse further increased for IKZF1plus patients. These alterations characterize subgroups of DS-ALL patients who need tailored therapeutic strategies.

NTRK2-243aa-encoded by circNTRK2-phosphorylated PAX5 at Y102, leading to the attenuation of the half-life of PAX5, as validated by in vitro kinase and MG132 rescue assays...Finally, overexpression of MBNL1 and circNTRK2 combined with PAX5 knockdown effectively inhibited the formation of GBM xenograft tumors and significantly prolonged the survival of orthotopic nude mice. We have delineated that the MBNL1/circNTRK2/PAX5 pathway plays a crucial role in regulating GBM glycolysis and could provide potential targets and alternative strategies for the treatment of GBM.

P1/2, N=23, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting

As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.

P1/2, N=23, Not yet recruiting, City of Hope Medical Center | Initiation date: Dec 2021 --> Jun 2022