Article
Pharmacology & Pharmacy
Han Han, Chen Zhao, Mengchen Liu, Hongxuan Zhu, Fancheng Meng, Ying Zhang, Guibin Wang, Li Wang, Lijun Di, Simon Mingyuen Lee, Qingwen Zhang, Guozhen Cui
Summary: This study evaluated the anti-leukemic activity of Homoharringtonine (HHT) in chronic myeloid leukemia (CML) and discovered its effectiveness against T315I mutant cells. Proteomic analysis revealed that HHT disrupted oxidative phosphorylation (OXPHOS) pathway by downregulating proteins in mitochondrial complex I (MCI). The findings present a novel therapeutic strategy to overcome BCR-ABL T315I mutation resistance.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Cell Biology
Veerandra Kumar, Jyotirmayee, Malkhey Verma
Summary: Modern clinical therapy of chronic myeloid leukemia (CML) with TKIs is highly efficacious in most patients, but is limited by intolerance or resistance. The clinical treatment of CML is a major challenge, and there is a need for new treatment strategies to overcome resistance or intolerance.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Daniela Damiani, Mario Tiribelli
Summary: The prognosis of acute myeloid leukemia (AML) remains unsatisfactory due to poor response to therapy or relapse, which can be attributed to the over-expression of multidrug resistance (MDR) proteins. ABCG2, an efflux transporter responsible for inducing MDR in leukemic cells, has the ability to extrude many antineoplastic drugs, leading to AML resistance and/or relapse. This review focuses on the expression and role of ABCG2, as well as its regulation and potential inhibition to counteract drug resistance and improve outcomes in AML patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Manuela Labbozzetta, Paola Poma, Monica Notarbartolo
Summary: Acute myeloid leukemia (AML) is difficult to treat due to the development of resistance to both traditional chemotherapy and new drugs in some patients. Multidrug resistance (MDR) in AML is often caused by the overexpression of P-glycoprotein (P-gp), which is an efflux pump. This mini-review focuses on the advantages of using natural substances as inhibitors of P-gp, including phytol, curcumin, lupeol, and heptacosane, and their mechanisms of action in AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Cell & Tissue Engineering
Malini Gupta, Britta Will
Summary: Adaptive aberrant gene regulation is a hallmark of malignant growth and therapy resistance in acute myeloid leukemia (AML). In this study, Eagle et al. identified oncogenic enhancer-driven overexpression of selenophosphate synthetase 2 (SEPHS2) as a targeted opportunity for mitigating malignant cell growth in AML.
Review
Oncology
Benjamin Lebecque, Celine Bourgne, Veronique Vidal, Marc G. Berger
Summary: In Chronic Myeloid Leukemia, DNA methylation abnormalities play a critical role in treatment response and disease progression risk, potentially serving as new therapeutic biomarkers. Studies have shown widespread DNA methylation abnormalities present early in CML diagnosis, offering insights for the development of novel treatment strategies.
Article
Cell Biology
Mohammad Houshmand, Nicoletta Vitale, Francesca Orso, Alessandro Cignetti, Ivan Molineris, Valentina Gaidano, Stefano Sainas, Marta Giorgis, Donatella Boschi, Carmen Fava, Alice Passoni, Marta Gai, Massimo Geuna, Federica Sora, Alessandra Iurlo, Elisabetta Abruzzese, Massimo Breccia, Olga Mulas, Giovanni Caocci, Fausto Castagnetti, Daniela Taverna, Salvatore Oliviero, Fabrizio Pane, Marco Lucio Lolli, Paola Circosta, Giuseppe Saglio
Summary: The study shows that the newly developed DHODH inhibitor, Meds433, is highly effective in targeting CML cells by activating the apoptotic pathway and inducing metabolic stress. This finding suggests that DHODH inhibition is a promising approach for targeting CML stem/progenitor cells.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Iga Stukan, Marek Gryzik, Grazyna Hoser, Andrew Want, Wioleta Grabowska-Pyrzewicz, Mikolaj Zdioruk, Mariola Napiorkowska, Marcin Cieslak, Karolina Krolewska-Golinska, Barbara Nawrot, Grzegorz Basak, Urszula Wojda
Summary: Chemotherapy is widely used for cancer treatment but often leads to therapy resistance. This study discovered that the novel compound BK124.1 can overcome chemotherapy resistance in chronic myeloid leukemia. BK124.1 showed efficacy in animal and cellular models, targeting multidrug resistant leukemia blasts and cancer stem cells. Future development of BK124.1 could offer a cure for chronic myeloid leukemia and other chemotherapy-resistant cancers.
Article
Medicine, Research & Experimental
De-long Wu, Yun Wang, Ting-juan Zhang, Ming-qiang Chu, Zi-jun Xu, Qian Yuan, Ji-chun Ma, Jiang Lin, Jun Qian, Jing-dong Zhou
Summary: Hypermethylation of the SLIT2 promoter is correlated with disease progression in CML, and it may function by regulating the expression of the SLIT2-embedded non-coding genes SLIT2-IT1 and miR-218 during CML progression.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Simona Sucha, Ales Sorf, Martin Svoren, Dimitrios Vagiannis, Fahda Ahmed, Benjamin Visek, Martina Ceckova
Summary: This study evaluated the clinical relevance of ABCB1 in AML patients and found that overexpression of ABCB1 was associated with adverse prognosis. Midostaurin, as an ABCB1 inhibitor, increased the accumulation of anthracyclines in AML patients and promoted apoptosis in leukemic cells. Additionally, miR-9 was identified as a useful prognostic marker in AML.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Cell Biology
Veerandra Kumar, Priyanka Singh, Sonu Kumar Gupta, Villayat Ali, Malkhey Verma
Summary: Different TKIs approved for CML have unique pharmacological properties, with drugs like asciminib showing effectiveness in resistant cases and having distinct metabolic pathways. Each TKI presents specific toxicities, such as ponatinib and asciminib being associated with metabolism-related toxicity.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Cell Biology
Angela Ianniciello, G. Vignir Helgason
Summary: Minimal residual disease (MRD) is the main cause of relapse in solid cancers and leukemias. In chronic myeloid leukemia (CML), autophagy plays a crucial role in maintaining the survival of drug resistant leukemic stem cells. Inhibition of autophagy-initiating kinase ULK1 could lead to stress-induced differentiation of leukemic stem cells, making them sensitive to drug treatment, providing a promising strategy for selective eradication of leukemic stem cells in CML patients.
Article
Biochemistry & Molecular Biology
Rachid Lahlil, Anne Aries, Maurice Scrofani, Celine Zanetti, Desline Hennequin, Bernard Drenou
Summary: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene. Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) has significantly improved clinical outcomes for CML patients, but IM resistance remains a major challenge. The cause of IM resistance in CML cells is unclear, but additional genetic alterations in leukemic stem cells (LSCs) are a common cause of relapse. A study found that a rare subpopulation of stem cells called very small embryonic-like stem cells (VSELs) in adult CML patients is resistant to IM and less sensitive to apoptosis compared to leukemic hematopoietic stem cells (HSCs). The expression levels of certain miRNAs are also affected in these IM-resistant VSELs, including miR-126 and miR-21, which are involved in LSC leukemia-initiating capacity and growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Instruments & Instrumentation
Qian Zhang, Minlu Ye, Lingyan Wang, Dongmei Jiang, Shuting Yao, Donghong Lin, Yang Chen, Shangyuan Feng, Ting Yang, Jianda Hu
Summary: This study explores the use of laser tweezers Raman spectroscopy for analyzing chemoresistance in chronic myeloid leukemia cells, demonstrating its high specificity and sensitivity as a novel analytical strategy. The research identifies important spectral features and metabolic pathways that can help distinguish different chemoresistance statuses.
APPLIED SPECTROSCOPY
(2021)
Review
Oncology
Adelina Fernandes, Naranie Shanmuganathan, Susan Branford
Summary: This article discusses the genomic mechanisms of drug resistance in patients with chronic myeloid leukemia (CML), emphasizing the impact of genetic mutations on treatment response and drug resistance, as well as the potential role of expanded genomic testing in managing CML patients in the future.