Aberrant DNA methylation of tumor suppressor genes has been reported in all major types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. However, most of the previous reports did not show the extent of concurrent methylation of multiple genes in the four leukemia types. Here, we analyzed six key genes (p14, p15, p16, p53, DAPK and TMS1) for DNA methylation using methylation specific PCR to analyze peripheral blood of 78 leukemia patients (24 CML, 25 CLL, 12 AML, and 17 ALL) and 24 healthy volunteers. In CML, methylation was detected for p15 (11%), p16 (9%), p53 (23%) and DAPK (23%), in CLL, p14 (25%), p15 (19%), p16 (12%), p53 (17%) and DAPK (36%), in AML, p14 (8%), p15 (45%), p53 (9%) and DAPK (17%) and in ALL, p15 (14%), p16 (8%), and p53 (8%). This study highlighted an essential role of DAPK methylation in chronic leukemia in contrast to p15 methylation in the acute cases, whereas TMS1 hypermethylation was absent in all cases. Furthermore, hypermethylation of multiple genes per patient was observed, with obvious selectiveness in the 9p21 chromosomal region genes (p14, p15 and p16). Interestingly, methylation of p15 increased the risk of methylation in p53, and vice versa, by five folds (p=0.03) indicating possible synergistic epigenetic disruption of different phases of the cell cycle or between the cell cycle and apoptosis. The investigation of multiple relationships between methylated genes might shed light on tumor specific inactivation of the cell cycle and apoptotic pathways.
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http://dx.doi.org/10.7314/apjcp.2014.15.1.75 | DOI Listing |
Clin Cancer Res
January 2025
Moffitt Cancer Center, Tampa, Florida, United States.
Purpose: Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared to tumors with lower RAS---RAF interaction.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
Purpose: This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose.
View Article and Find Full Text PDFDiscov Oncol
January 2025
School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Background: Nucleolar protein 7 (NOL7), a specific protein found in the nucleolus, is crucial for maintaining cell division and proliferation. While the involvement of NOL7 in influencing the unfavorable prognosis of metastatic melanoma has been reported, its significance in predicting the prognosis of patients with Hepatocellular Carcinoma (HCC) remains unclear.
Methods: Aberrant expression of NOL7 in HCC and its prognostic value were evaluated using multiple databases, including TCGA, GTEx, Xiantao Academic, HCCDB, UALCAN, TISCH, and STRING.
Bot Stud
January 2025
Department of Life Sciences, National Chung Hsing University, Taichung, 40227, Taiwan.
Ice plant (Mesembryanthemum crystallinum L.) is a halophyte and an inducible CAM plant. Ice plant seedlings display moderate salt tolerance, with root growth unaffected by 200 mM NaCl treatments, though hypocotyl elongation is hindered in salt-stressed etiolated seedlings.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Materdicine Lab, School of Life Sciences, Shanghai University, 200444 Shanghai, P. R. China.
The presence of a substantial necrotic core in atherosclerotic plaques markedly heightens the risk of rupture, a consequence of elevated iron levels that exacerbate oxidative stress and lipid peroxidation, thereby sustaining a detrimental cycle of ferroptosis and inflammation. Concurrently targeting both ferroptosis and inflammation is crucial for the effective treatment of vulnerable plaques. In this study, we introduce gallium hexacyanoferrate nanoabsorption catalysts (GaHCF NACs) designed to disrupt this pathological cycle.
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