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Decoding RNA Metabolism by RNA-linked CRISPR Screening in Human Cells.
bioRxiv
July 2024
Basic Sciences Division and Computational Biology Section of the Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle WA, USA.
RNAs undergo a complex choreography of metabolic processes in human cells that are regulated by thousands of RNA-associated proteins. While the effects of individual RNA-associated proteins on RNA metabolism have been extensively characterized, the full complement of regulators for most RNA metabolic events remain unknown. Here we present a massively parallel RNA-linked CRISPR (ReLiC) screening approach to measure the responses of diverse RNA metabolic events to knockout of 2,092 human genes encoding all known RNA-associated proteins.
View Article and Find Full Text PDFOncogenic dependency on SWI/SNF chromatin remodeling factors in T-cell acute lymphoblastic leukemia.
Leukemia
September 2024
Cancer Science Institute of Singapore, National University of, Singapore, 117599, Singapore.
Article Synopsis
- T-cell acute lymphoblastic leukemia (T-ALL) arises from immature thymocytes, and while transcription factors like NOTCH1 and MYC are well-studied, the role of chromatin remodeling factors in T-ALL is less understood.
- Integrative analysis revealed that the SWI/SNF chromatin remodeling complex, particularly its subunit SMARCA4, is highly expressed in T-ALL patient samples, and its loss leads to cell apoptosis and growth inhibition.
- Furthermore, the impaired function of SMARCA4 significantly impacts key pathways like NOTCH1-MYC, highlighting potential new therapeutic targets for T-ALL treatment.
Acute Lymphoblastic Leukemia in Pregnant Ovarian Hypersensitivity Syndrome.
Clin Nucl Med
August 2024
From the Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Ovarian hyperstimulation syndrome (OHSS) is characterized by cystic enlargement of the ovaries and a fluid retention. This syndrome is sometimes caused after in vitro fertilization. We treated a 37-year-old woman with OHSS after in vitro fertilization, coincidentally complicated with acute lymphoblastic leukemia.
View Article and Find Full Text PDFAsparagine transport through SLC1A5/ASCT2 and SLC38A5/SNAT5 is essential for BCP-ALL cell survival and a potential therapeutic target.
Br J Haematol
July 2024
Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Parma, Italy.
B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) blasts strictly depend on the transport of extra-cellular asparagine (Asn), yielding a rationale for L-asparaginase (ASNase) therapy. However, the carriers used by ALL blasts for Asn transport have not been identified yet. Exploiting RS4;11 cells as BCP-ALL model, we have found that cell Asn is lowered by either silencing or inhibition of the transporters ASCT2 or SNAT5.
View Article and Find Full Text PDFInvestigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment.
Nat Commun
May 2024
Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Defining genetic factors impacting chemotherapy failure can help to better predict response and identify drug resistance mechanisms. However, there is limited understanding of the contribution of inherited noncoding genetic variation on inter-individual differences in chemotherapy response in childhood acute lymphoblastic leukemia (ALL). Here we map inherited noncoding variants associated with treatment outcome and/or chemotherapeutic drug resistance to ALL cis-regulatory elements and investigate their gene regulatory potential and target gene connectivity using massively parallel reporter assays and three-dimensional chromatin looping assays, respectively.
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