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Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival.
Cell Commun Signal
January 2025
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems.
View Article and Find Full Text PDFUnveiling the omics tapestry of B-acute lymphoblastic leukemia: bridging genomics, metabolomics, and immunomics.
Sci Rep
January 2025
Division of Hematology, Second Xiang-ya Hospital, Central South University, Changsha, China.
Acute B-lymphoblastic leukemia (B-ALL) is a highly heterogeneous hematologic malignancy, characterized by significant molecular differences among patients as the disease progresses. While the PI3K-Akt signaling pathway and metabolic reprogramming are known to play crucial roles in B-ALL, the interactions between lipid metabolism, immune pathways, and drug resistance remain unclear. In this study, we performed multi-omics analysis on different patient cohorts (newly diagnosed, relapsed, standard-risk, and poor-risk) to investigate the molecular characteristics associated with metabolism, signaling pathways, and immune regulation in B-ALL.
View Article and Find Full Text PDFIdentification of a novel TOP2B::AFF2 fusion gene in B-cell acute lymphoblastic leukemia.
Sci Rep
January 2025
Department of Hematology and Oncology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Children's Hospital of Chongqing Medical University, No 136 Zhongshan 2 road, YuZhong district, Chongqing, 400014, China.
Genetic alterations play a pivotal role in leukemic clonal transformation, significantly influencing disease pathogenesis and clinical outcomes. Here, we report a novel fusion gene and investigate its pathogenic role in acute lymphoblastic leukemia (ALL). We engineer a transposon transfection system expressing the TOP2B::AFF2 transcript and introduce it into Ba/F3 cells.
View Article and Find Full Text PDFLongitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.
Nat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
View Article and Find Full Text PDFEpidemiology, Treatment Outcomes, and Prognosis of Myelodysplastic Syndromes/Neoplasms in Taiwan: Real-World Insights and Trends.
Clin Lymphoma Myeloma Leuk
January 2025
Divisions of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Background: Myelodysplastic syndromes/neoplasms (MDS) are a diverse group of clonal myeloid disorders. Advances in molecular technology lead to the development of new classification systems. However, large-scale epidemiological studies on MDS in Asian countries are currently scarce.
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