Leukemia research papers

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Clathrin-associated SCYL2 contributes to the activation of PI3K/AKT signaling and tumorigenesis through PTEN phosphorylation in adult T-cell leukemia/lymphoma. reports: Inactivation of PTEN by post-translational modifications causes aberrant amplification of the PI3K/AKT signaling pathway in many tumors. PTEN is a tumor suppressor phosphatase that is frequently phosphorylated at conserved serine/threonine residues (S380, T382, and T383 clusters) in the C-terminal tail of ATL and various solid cancer cells. Here, we identify SCY1-like protein 2 (SCYL2), with a protein kinase-like domain, as a novel PTEN-binding protein; however, the mechanism by which SCYL2 regulates PTEN phosphorylation remains unclear.

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Design, Synthesis, and Structure-Activity Relationship Studies of 7 H ‑Pyrrolo[2,3‑ d ]pyrimidine Derivatives as Potent Casein Kinase 1α (CK1α) Inhibitors. reports: Casein kinase 1α (CK1α) is a serine/threonine kinase that plays a pivotal role in regulating p53 and other critical signaling pathways and is intimately involved in tumor initiation and progression. Inhibition of CK1α has been demonstrated to be a promising therapeutic strategy for certain types of cancers such as acute myeloid leukemia (AML). In this study, we designed and synthesized a series of novel CK1α inhibitors bearing a 7 H -pyrrolo-[2,3- d ]-pyrimidine scaffold.

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Identification of GTF2IRD1 as a novel transcription factor essential for acute myeloid leukemia reports: Acute myeloid leukemia (AML) is an aggressive blood malignancy characterized by clonal accumulation of immature myeloid progenitors in the bone marrow and peripheral blood. Transcription factors are the most frequently mutated and dysregulated genes in AML, and they have critical roles in AML pathogenesis and progression. In this study, we performed large-scale RNA interference screens in MLL-AF9-transformed AML cells and identified GTF2IRD1 as a novel transcription factor essential for the survival of various types of myeloid leukemic cells in vitro and in vivo, but not for primary normal hematopoietic cells. This is a preprint and not peer reviewed.

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Genome-wide annotation of gene regulatory elements linked to cell fitness reports: Noncoding regulatory elements control gene expression and thus govern nearly all biological processes. Epigenomic profiling assays have identified millions of putative regulatory elements, but systematically determining the function of those regulatory elements remains a substantial challenge. Here we adapt CRISPR screening by epigenetic repression to screen all 111,619 putative non-coding regulatory elements defined by open chromatin sites in human K562 leukemia cells for their role in regulating essential cellular processes and proliferation. This is a preprint and not peer reviewed.

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Clofazimine treatment modulates key non-coding RNAs associated with tumor progression and drug resistance in lethal Prostate Cancer reports: Prostate cancer (PCa) is the most commonly diagnosed cancer and the second-leading cause of cancer death among men in the United States, representing 24.3% of all new cancer cases in the US. Metastatic castration-resistant prostate cancer (mCRPC) is a clinically advanced form of PCa that is associated with increased aggressiveness, cancer stemness, morbidity, and the risk of developing resistance to taxanes, currently the first-line chemotherapeutic agents for mCRPC.Development of new target-directed drugs to treat mCRPC poses significant challenges, given the recognition that monospecific inhibitors have limited efficacy. Hence, there is an urgent medical need to develop new strategies that block major oncogenic signaling pathways driving the most lethal forms of PCa. This is a preprint and not peer reviewed.

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Cancer and Post-therapy Cardiotoxicity Risk in Adolescents, Young Adults, and Adults with Down Syndrome reports: The median life expectancy of people with Down syndrome has increased substantially over the past several decades, from 4 years in 1970 to 53 years in 2010. Despite the recent improvement in survival, there is little data about the prevalence of age-related diseases, including age-related malignancies, and the impact of standard cancer treatments on cardiovascular health. We retrospectively reviewed medical records for age- and sex-matched patients [≥]15 years old with and without Down syndrome using the TriNetX platform to identify the prevalence of malignancies and explore cardiovascular outcomes after treatment with anthracyclines. This is a preprint and not peer reviewed.

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Analysis of Multiple Myeloma Drug Efficacy reports: IntroductionMultiple myeloma (MM) is an incurable plasma cell neoplasm. MM-specific alterations in methylation status cause gradual epigenetic changes and lead to pre-MM disease states, such as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering MM (SMM). The communication between MM cells and the bone marrow (BM) stromal cells serves a pivotal role in MM development by supporting transformed cell growth and proliferation. This is a preprint and not peer reviewed.

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Necrotizing soft tissue infection of the fingertips secondary to paronychia in a leukemic child: a case report and warning. reports: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, for which chemotherapy remains the cornerstone of treatment. Skin toxicity is a frequent adverse reaction to chemotherapy; however, progression from paronychia to necrotizing soft tissue infection of the fingertips is uncommon. This report describes the case of a 7-year-old child with ALL who developed paronychia following combination chemotherapy with vincristine and daunorubicin.

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