Acute leukemia is characterized by clonal heterogeneity that contributes to poor drug responses in patients. Despite treatment advances, the occurrence of relapse remains a major barrier to achieving cures as current therapeutic approaches are inadequate to effectively prevent or overcome resistance. Given that only a few genetic mutations are associated with relapse in acute leukemia patients, there is a growing focus on 'non-genetic' mechanisms that affect the hallmarks of cancer to allow leukemic cells to survive post therapy. In this review, we provide an overview of the therapeutic landscape in acute leukemias. Importantly, we discuss non-genetic mechanisms exploited by leukemic cells to promote their survival after treatment. Last, we present current strategies to prevent or overcome drug resistance in this disease.
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http://dx.doi.org/10.1016/j.trecan.2023.09.003 | DOI Listing |
Cancer cells within tumors exhibit a wide range of phenotypic states driven by non-genetic mechanisms in addition to extensively studied genetic alterations. Conversions among cancer cell states can result in intratumoral heterogeneity which contributes to metastasis and development of drug resistance. However, mechanisms underlying the initiation and/or maintenance of such phenotypic plasticity are poorly understood.
View Article and Find Full Text PDFHeredity (Edinb)
January 2025
Department of Biological Sciences, University of South Carolina, Columbia, SC, USA.
Maternal effects have been shown to play influential roles in many evolutionary and ecological processes. However, understanding how environmental stimuli induce within-generation responses that transverse across generations remains elusive, particularly when attempting to segregate confounding effects from offspring genotypes. This review synthesizes literature regarding resource- and predation-driven maternal effects in the model system Daphnia, detailing how the maternal generation responds to the environmental stimuli and the maternal effects seen in the offspring generation(s).
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
January 2025
Department of Physiology & Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106.
Regulators of G protein signaling (RGS) proteins finetune signaling via heterotrimeric G proteins to maintain physiologic homeostasis in various organ systems of the human body including the brain, kidney, heart, and the vasculature. Impaired regulation of G protein signaling by RGS proteins is implicated in the pathogenesis of several human diseases including various forms of cardiomyopathy such as hypertrophic cardiomyopathy and dilated cardiomyopathy (DCM). Both genetic and non-genetic changes that impinge on G protein signaling in cardiomyocytes are implicated in the etiology of DCM, and there is accumulating evidence that such genetic and non-genetic changes affecting G protein signaling in cell types other than cardiomyocytes could serve as a DCM trigger in humans.
View Article and Find Full Text PDFRes Sq
December 2024
The Metrohealth System, Case Western Reser.
Long non-coding RNAs (lncRNAs) and RNA N6-methyladenosine (mA) have been linked to leukemia drug resistance. However, whether and how lncRNAs and mA coordinately regulate resistance remain elusive. Here, we show that many differentially expressed lncRNAs enrich mA, and more lncRNAs tend to have higher mA content in CML cells resistant to tyrosine kinase inhibitors (TKIs).
View Article and Find Full Text PDFJ Hepatol
January 2025
Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom. Electronic address:
Background & Aims: Hepatocyte transplantation has shown promise for genetic diseases of the hepatocytes but to date has shown limited efficacy for non-genetic forms of severe liver injury. Limited cell engraftment and poor function of donor hepatocytes in recipient livers impacts the clinical utility of hepatocyte cell therapy. The mechanisms underpinning this are poorly understood.
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