Brian J. Abraham's research while affiliated with St. Jude Children's Research Hospital and other places

... Furthermore, FNRMS-like Subgroups 4 and 5 exhibited the expression of genes defining vascular system (Supplementary Table 3), in line with previous reports indicating an endothelial cell as an origin of cells for FNRMS 17 . Conversely, higher expression of genes indicating skeletal muscle in Subgroup 3 may reflect myogenic reprogramming driven by the PAX3-FOXO1 fusion gene of FPRMS 18 . These results support the idea that the development of both RMS subtypes aligns with muscle development and each subtype employs specific transcriptional programs at its different stages To test whether the distinct molecular features of the most FPMRS-like Subgroup 3 and the most FNRMS-like Subgroup 4 mirror underlying differential features between RMS subtypes, we investigated DEGs in the subgroups (Supplementary Table 2 Table 5 and 6) followed by GO analysis. ...

... 36 These enhancers, activated by singular kinds of factors are common among developmental and lineage-determining TFs, but are less understood for constitutive housekeeping TFs like BMAL1 and CLOCK. 37,38 In an analysis of super enhancers (SEs) in TNBC, a group of TF binding motifs including E-box was identified to constitute the SEs. 23 Although currently we have no evidence to support that this is a SE-mediated mechanism, this finding inspired us to hypothesize that strong CREs in TNBC can be activated and maintained by multiple TFs in the absence of a singular master driver. ...

... Communication between the TME and tumour cells shapes the cancer epigenome, which encompasses posttranslational modifications in DNA, histones and other chromatin-associated proteins. These alterations can leave long-lasting marks that affect both transcription 99 and translation 100 of CSCs. Although they often elicit similar outcomes on cellular behaviours, epigenetic modifications differ from genetic mutations in that they are potentially reversible, making this an interesting field for developing anticancer therapies in the future 101 . ...

... Importantly, Myc directly contributes to the SRR2 reporter activity and CSL phenotype in RR cells. While Myc is one of the most implicated oncoproteins in human cancer [27][28][29][30], its pathogenetic roles in ALK+ALCL have not been well-defined, although a handful of previous studies have shown that Myc is a downstream target of NPM-ALK via STAT3 signaling [31,32]. Because Myc contributes to the CSL phenotype of RR cells, we believe that it is highly relevant to investigate the mechanism underlying the differential Myc protein levels between RU and RR cells. ...

... It is The copyright holder for this preprint this version posted June 3, 2024. Importantly, we found an upregulation of the PDGFRB-STAT5-IL10 oncogenic axis, which was recently shown to be crucial for the aggressiveness of ALK+ ALCL 56 . In (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. ...

... The final version may differ from this version. He, Zan et al., 2022;Liu, Qian et al., 2022;Peter, Eisenwort et al., 2022;Piya, Yang et al., 2022;Wang, Xu et al., 2022;Yang, Hu et al., 2022;Zhang, Peng et al., 2022;Zhang, Gao et al., 2022;He, Ju et al., 2023;Huang, Yao et al., 2023;Ivanov, Milosevic Feenstra et al., 2023;Kim, Choi et al., 2023;Liu, Chen et al., 2023;Rose, Fleming et al., 2023;Wang, Li et al., 2023). In addition, BET inhibitors have also been used in combination with AKT inhibitors, PARP inhibitors, and BCL-2 inhibitors, demonstrating impressive therapeutic effects on tumors (Bevill, Olivares-Quintero et al., 2019;Tian, Chen et al., 2019;Fehling, Miller et al., 2020;Lee, Kang et al., 2020;Shigeta, Lui et al., 2021;Zhang, Cai et al., 2021). ...

... Epigenetic dysregulation of transcription is common in cancer cells, resulting in transcriptional amplification, developmental arrest and oncogenesis 55 . These processes are mediated by cohorts of transcription factors and coregulators, which cumulatively result in a cancer phenotype 55,56 . Broad efforts to target these dysregulated processes have yielded agents that can suppress transcription (reviewed in 1 ). ...

... 64 Significant progress has been achieved in identifying molecular pathways necessary for fetal hepatocyte maturity, and subsequent optimized culture conditions have enabled considerable progresses in PSC-derived HLCs. 65 Hence, culture conditions for liver organoid models can similarly be optimized in the future to enhance the functional maturity of cells. • Wolman disease ...

... Emerging small-molecule inhibitors that target the SE have been demonstrated in clinical trials to exert a notable effect on cancer treatment [12,13]. Recent studies reported that the disturbance of the SE complex by co-targeting of BRD4 and CDK7 might be a promising therapeutic treatment against cancers including head and neck squamous cell carcinoma, pancreatic ductal adenocarcinoma (PDAC) and neuroblastoma [14][15][16]. However, whether BRD4 and CDK7 could be synergistic targets for the treatment of HCC remains largely unexplored. ...

... Lineage-dependency mechanisms often involve lineage-specific master regulatory genes 2,10 . Thus, one current approach to identify critical therapeutic targets is to delineate key transcriptional machinery dependencies 11 . ...