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Chronic Lymphocytic Leukemia (CLL) is characterized by clinical and biological heterogeneity, with a subset of patients progressing to Richter Transformation (RT), an aggressive lymphoma. This study explores MYC target gene activation across various CLL stages and disease subgroups using bulk RNAseq and single-cell RNAseq data. Our findings reveal increased MYC activation in unmutated IGHV CLLs, trisomy 12 cases, and RT stages. In RT, MYC activation is independent of B-cell receptor signaling, correlating instead with cell cycling and TLR9 interactions, indicating alternative survival mechanisms. High MYC activation correlates with shorter time to first treatment and enhances tumor microenvironment interactions, particularly with myeloid cells. These results underscore MYC's significant role in CLL progression and RT, supporting MYC's potential as a target for stratifying CLL patients and developing therapeutic strategies.
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http://dx.doi.org/10.3389/fphar.2025.1642458 | DOI Listing |
Cell Signal
September 2025
Departments of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address:
Mature mRNAs are generated by spliceosomes that recruit factors to aid RNA splicing in which introns are removed and exons joined. Among the splicing factors, a family of proteins contain a homologous U2 Auxiliary Factor (U2AF) Homology Motif (UHM) to bind with factors containing U2AF ligand motifs (ULM) and recruit them to regulate 3' splice site selection. Mutations and overexpression of UHM splicing factors are frequently found in cancers.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Immune Response and Immunotherapy, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, GIBH-CUHK Joint Resea
TP53 mutations are highly associated with hepatocellular carcinoma (HCC), a common and deadly cancer. However, few primary drivers in the progression of HCC with mutant TP53 have been identified. To uncover tumor suppressors in human HCC, a genome-wide CRISPR/Cas9-based screening of primary human hepatocytes with MYC and TP53 overexpression (MT-PHHs) is performed in xenografts.
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Reproductive Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Snai2 is a transcription factor that inhibits the proliferation of cervical cancer cells and tumor growth. The expression of Snai2 inhibited the expression of β-catenin and impaired Wnt/β-catenin signaling pathway activity. The results of the RNA sequence in Snai2-overexpressing cervical cancer cells implied a strong correlation between Snai2 and TRIM31 with ubiquitin ligase activity.
View Article and Find Full Text PDFCureus
August 2025
Dermatology, Centro Medico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City, MEX.
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), is an uncommon and aggressive subtype of cutaneous B-cell lymphoma, typically affecting elderly women and predominantly involving the lower extremities. Its diagnosis relies on immunohistochemical profiling and clinical presentation. We report a rare case of a 45-year-old male presenting initially with scalp and supraciliary plaques.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
August 2025
Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, 750004 Yinchuan, Ningxia Hui Autonomous Region, China.
Background: Mediator complex subunit 10 (MED10) serves as a critical regulator of eukaryotic gene expression by facilitating RNA polymerase II activity. Our investigation aims to characterize MED10's functional contributions and underlying molecular pathways in hepatocellular carcinoma (HCC) development.
Methods: MED10 expression patterns in HCC and their correlation with clinicopathological parameters and patient outcomes were examined using bioinformatics databases and immunohistochemistry.