Acute myeloid leukemia (AML) is the second most common leukemia among children. Although significant progress in AML therapy has been achieved, treatment failure is still associated with poor prognosis, emphasizing the need for novel, innovative therapeutic approaches. To address this major obstacle, extensive knowledge about leukemogenesis and the complex interplay between leukemic cells and their microenvironment is required. The tremendous role of this bone marrow microenvironment in providing a supportive and protective shelter for leukemic cells, leading to disease development, progression, and relapse, has been emphasized by recent research. It has been revealed that the interplay between leukemic cells and surrounding cellular as well as non-cellular components is critical in the process of leukemogenesis. In this review, we provide a comprehensive overview of recently gained knowledge about the importance of the microenvironment in AML whilst focusing on promising future therapeutic targets. In this context, we describe ongoing clinical trials and future challenges for the development of targeted therapies for AML.
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http://dx.doi.org/10.3390/children8050371 | DOI Listing |
Biomark Res
January 2025
Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
Although chimeric antigen receptor (CAR) T cell therapy has shown remarkable efficacy against leukemic cells, it still has critical limitations. CAR macrophage has been regarded as a potential alternative to CAR T cells. However, due to the difficulties in gene transduction into macrophages, the production of primary human CAR macrophages from peripheral blood mononuclear cells (PBMC) using lentivirus is highly challenging.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, United States.
Polycomb Repressive Complex 1 (PRC1) is associated with transcriptional silencing, and its dysregulation plays an important role in various cancers. Well-characterized PRC1 inhibitors can facilitate the exploration of PRC1 inhibition as therapeutic agents. By employing an NMR-based fragment screening approach, we have previously identified a very weak millimolar ligand , which directly binds to RING1B-BMI1.
View Article and Find Full Text PDFEur J Med Chem
December 2024
INSERM UMR 1100 CEPR, Research Center for Respiratory Diseases, Team 2 "Proteolytic Enzymes and Their Pharmacological Targeting in Lung Diseases", 10 Boulevard Tonnellé, 37032, Tours, France. Electronic address:
Signal Transdcer and Activator of Transcription 5A and 5B (STAT5A/5B) are key effectors of tyrosine kinase oncogenes in myeloid leukemias. It is now clearly evidenced that inhibition of STAT5A/5B not only blocks the growth and survival of myeloid leukemia cells but also overcomes the resistance of leukemic cells to chemotherapy. Previous screening experiments allowed us to identify 17f as a lead compound with promising antileukemic activity that blocks the phosphorylation and transcriptional activity of STAT5A/5B in myeloid leukemia cells addicted to these proteins.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
December 2024
Blood Disease Institute, Xuzhou Medical University,Xuzhou 221000, Jiangsu Province, China.
Objective: To harvest the primary Philadelphia chromosome-positive (Ph) cells of B-acute lymphoblastic leukemia (B-ALL) and to establish the B-ALL mouse model.
Methods: The plasmid carrying fusion gene was transferred into the bone marrow(BM) cells of C57BL/6J mice by retrovirus. Syngeneic mice irradiated with 9 Gy of Co γ-ray were injected with the transfected BM cells as the first generation (G1), and then the primary cells from the spleen and BM of the diseased mice were obtained and frozen.
Br J Clin Pharmacol
December 2024
Novartis Pharma AG, Basel, Switzerland.
Aims: This study aims to evaluate the exposure-efficacy relationship of nilotinib and longitudinal BCR::ABL1 levels in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase (CML-CP) and those who are imatinib-resistant or intolerant using a semimechanistic disease model.
Methods: The analysis included 489 CML-CP patients from 3 nilotinib trials (NCT00109707; NCT00471497; NCT01043874) with duration of follow-up ranging from 2 to 9 years. The semimechanistic disease model of CML-CP consisted of quiescent leukaemic stem cells, proliferating drug-susceptible and -resistant bone marrow cells.
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