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Large clones of Clonal Hematopoiesis affect outcome in Mantle Cell Lymphoma: Results from The FIL MCL0208 Clinical Trial.
Blood Adv
January 2025
Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
Although recent evidence suggests that myeloid clonal hematopoiesis (M-CH) may influence lymphoma clinical outcome, its impact in mantle cell lymphoma (MCL) remains unclear. Here, we report a comprehensive NGS-based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT02354313), evaluating lenalidomide maintenance versus observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young MCL patients. Overall, 254/300 (85%) enrolled patients (median age 57 years [32-66]) had a baseline sample available for CH analysis.
View Article and Find Full Text PDFIncreased clonal hematopoiesis in long-term survivors of pediatric hematopoietic cell transplantation.
Blood Cancer Discov
January 2025
Princess Máxima Center, Utrecht, Netherlands.
In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. Here, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 non-transplanted controls. CH was detected in 16% of HCT recipients and 8% of controls, at variant allele frequencies (VAFs) of 0.
View Article and Find Full Text PDFClonal Hematopoiesis of Indeterminant Potential as a Predictor of Colorectal Cancer Risk: Insights from the UK Biobank Cohort.
Cancer Epidemiol Biomarkers Prev
January 2025
Southern Medical University, Guangzhou, China.
Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to be associated with the occurrence of solid tumors, but its relationship with colorectal cancer still needs to be studied.
Methods: We conducted a prospective matched case-control study using data from the UK Biobank, including 5,310 incident colorectal cancer (CRC) cases and 26,550 controls matched for age, sex, and body mass index (BMI).
Results: Analysis of the UK Biobank data revealed that the presence of CHIP was associated with an increased risk of CRC.
Unlabelled: is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML), and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing de-repression of silenced elements in heterochromatin.
View Article and Find Full Text PDFGene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibility and histone modifications. These complex networks have been shown to be disrupted during aging, disease, and cancer. However, profiling these networks across diverse cell types and states has been limited due to the technical constraints of existing methods for mapping DNA:Protein interactions in single cells.
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