Several groups have shown that that the BCR-ABL1 transcript level measured at 3 or 6 months after starting treatment with tyrosine kinase inhibitors strongly predicts clinical outcomes for patients with chronic myeloid leukemia. In this work, we asked whether the prognostic value of the 3-month transcript level could be improved by combining the 3- and 6-month results. We classified patients treated with imatinib and patients treated with dasatinib according to their transcript levels at 3 months and 6 months. The patients who met the 3-month landmark but failed the 6-month one had outcomes identical to those of patients who met both landmarks, whereas the patients who failed the first landmark but met the second one had prognoses similar to those who failed both landmarks. In summary, early intervention strategies can be based robustly just on the transcript level at 3 months. This trial was registered at www.clinicaltrials.gov as # NCT01460693.
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http://dx.doi.org/10.1182/blood-2012-11-466037 | DOI Listing |
Sci Adv
January 2025
Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Although lipid-derived acetyl-coenzyme A (CoA) is a major carbon source for histone acetylation, the contribution of fatty acid β-oxidation (FAO) to this process remains poorly characterized. To investigate this, we generated mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1, distal FAO enzyme) knockout macrophages. C-carbon tracing confirmed reduced FA-derived carbon incorporation into histone H3, and RNA sequencing identified diminished interferon-stimulated gene expression in the absence of ACAT1.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America.
Viral infections of the central nervous system (CNS) are a major cause of morbidity largely due to lack of prevention and inadequate treatments. While mortality from viral CNS infections is significant, nearly two thirds of the patients survive. Thus, it is important to understand how the human CNS can successfully control virus infection and recover.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Tigecycline (Tgc), a third-generation tetracycline is found as the last line of defense against multi-drug resistant bacteria. Recent increased rate of resistance to tgc, a human-restricted agent among animal bacteria poses a significant global health challenge. Overuse of first generation tetracyclines (Tet) and phenicols in animals have been suggested to be associated with Tgc resistance development.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China.
Spatially resolved transcriptomics (SRT) technologies facilitate the exploration of cell fates or states within tissue microenvironments. Despite these advances, the field has not adequately addressed the regulatory heterogeneity influenced by microenvironmental factors. Here, we propose a novel Spatially Aligned Graph Transfer Learning (SpaGTL), pretrained on a large-scale multi-modal SRT data of about 100 million cells/spots to enable inference of context-specific spatial gene regulatory networks across multiple scales in data-limited settings.
View Article and Find Full Text PDFBlood
January 2025
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States.
Stemness-associated cell states are linked to chemotherapy resistance in AML. We uncovered a direct mechanistic link between expression of the stem cell transcription factor GATA2 and drug resistance. The GATA-binding protein 2 (GATA2) plays a central role in blood stem cell generation and maintenance.
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