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Despite the therapeutic progress, relapse remains a major problem in the treatment of acute lymphoblastic leukemia (ALL). Most leukemia cells that survive chemotherapy are found in the bone marrow (BM), thus resistance to chemotherapy and other treatments may be partially attributed to pro-survival signaling to leukemic cells mediated by leukemia cell-microenvironment interactions. Adhesion of leukemia cells to BM stromal cells may lead to cell adhesion-mediated drug resistance (CAM-DR) mediating intracellular signaling changes that support survival of leukemia cells. In ALL and chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the PI3K/AKT signaling pathway has been shown to be critical in CAM-DR. PI3K targeting inhibitors have been approved for CLL and have been evaluated preclinically in ALL. However, PI3K inhibition has yet to be approved for clinical use in ALL. Here, we review the role of PI3K signaling for normal hematopoietic and leukemia cells and summarize preclinical inhibitors of PI3K in ALL.
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http://dx.doi.org/10.1007/978-3-031-06566-8_17 | DOI Listing |
Eur J Case Rep Intern Med
August 2025
Division of Hematology and Oncology, UNM Comprehensive Cancer Center, Albuquerque, USA.
Background: Blinatumomab and inotuzumab ozogamicin (InO) are B-cell targeted agents used in the frontline and relapsed/refractory treatment of B-cell acute lymphoblastic leukaemia (B-ALL). Blinatumomab, a bispecific T-cell engager that targets CD19 and CD3, and InO, an antibody-drug conjugate targeting CD22, have both shown efficacy. However, recent reports have noted lineage conversion as a complication when these agents are used individually or sequentially.
View Article and Find Full Text PDFEJHaem
October 2025
Division of Endocrinology Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine Graduate School of Medicine University of the Ryukyus Ryukyus Japan.
Introduction: We previously reported that sodium-glucose co-transporter 2 (SGLT-2) was ectopically overexpressed in adult T-cell leukemia (ATL) cells notably in aggressive type but in indolent type, and widely-used anti-diabetic SGLT-2 inhibitors (SGLT-2i) considerably attenuated proliferation of leukemic cells.
Methods: We performed retrospective analyses for 10 years to see whether SGLT-2i would prevent aggressive transformation in patients with indolent type ATL accompanied by diabetes. Nucleosome occupancy in the promotor region of the gene was also assessed to explore the possible involvement of epigenetic modification in such an ectopic overexpression.
Front Oncol
August 2025
Department Hematopathology, Shenzhen Hospital of Southern Medical University, Shenzhen, China.
Background: Mixed-phenotype acute leukemia (MPAL) is a rare acute leukemia for which data are currently not available to guide therapy. It has a poor outcome, particularly in elderly patients.
Case Presentation: We report the successful use of venetoclax/azacitidine as treatment for a treatment-naive elderly patient with early T-cell precursor (ETP)/myeloid MPAL.
Indian J Nucl Med
August 2025
Department of Nuclear Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India.
Acute lymphoblastic leukaemia (ALL) is a prevalent cause of paediatric leukaemia. Patients with ALL typically exhibit symptoms such as fever, bleeding, weight loss, and bone pain. Blood investigations results predominantly show anaemia and pancytopenia with blast cells in the peripheral smear.
View Article and Find Full Text PDFFood Sci Nutr
September 2025
Department of Nutrition Sciences, School of Health Larestan University of Medical Sciences Iran.
Chronic myeloid leukemia (CML), a myeloproliferative neoplasm, is characterized by the fusion gene, which results in constitutive tyrosine kinase activity. While tyrosine kinase inhibitors (TKIs) have significantly improved CML outcomes, resistance and the persistence of leukemic stem cells remain major clinical challenges. Curcumin, a natural polyphenol derived from , has demonstrated potential anticancer properties.
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