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  • Open Access

    ARTICLE

    Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction

    Angela Silvano*†1, Giulio Menegazzi*1, Silvia Peppicelli*1, Caterina Mancini*, Alessio Biagioni*, Alessandro Tubita*, Ignazia Tusa*, Jessica Ruzzolini*, Matteo Lulli*, Elisabetta Rovida*, Persio Dello Sbarba*

    Oncology Research, Vol.29, No.1, pp. 33-46, 2021, DOI:10.3727/096504022X16442289212164

    Abstract This study was directed to deepen the effects of nutrient shortage on BCR/Ablprotein expression and signaling in chronic myeloid leukemia (CML) cells. The backbone of the study was cell culture in medium lacking glucose, the consumption of which we had previously shown to drive BCR/Ablprotein suppression, and glutamine, the other main nutrient besides glucose. In this context, we focused on the role of lactate, the main by-product of glucose metabolism under conditions of rapid cell growth, in particular as a modulator of the maintenance of CML stem/progenitor cell potential, a crucial determinant of disease course More >

  • Open Access

    ARTICLE

    Anti-proliferative effects of a small molecule inhibitor of CDK AT7519 on chronic myeloid leukemia (CML) cells through halting the transition of cells from G2/M phase of the cell cycle

    MASOUMEH OGHABI1,2, AVA SAFAROGHLI-AZAR1,2, ATIEH POURBAGHERI-SIGAROODI1,2, MOHAMMAD SAYYADI3, MOHSEN HAMIDPOUR1, MOHAMMAD HOSSEIN MOHAMMADI1, DAVOOD BASHASH1,*

    BIOCELL, Vol.44, No.2, pp. 183-192, 2020, DOI:10.32604/biocell.2020.08880 - 27 May 2020

    Abstract Pathogenesis of chronic myeloid leukemia (CML) has mostly been studied with regard to the oncogenic role of BCR/ABL fusion; however, recent disclosures have declared that the challenges with the treatment of CML patients would not be resolved until the role of other aberrancies is ignored. Given the involvement of cyclin-dependent kinases (CDKs) in the pathogenesis of CML, the present study aimed to investigate the effects of a multi-CDK inhibitor AT7519 on BCR/ABL-harboring CML-derived K562 cells. Our results showed that AT7519 effectively reduced the survival of K562 and induced its anti-proliferative effect through the induction of… More >

  • Open Access

    REVIEW

    What Is the Optimal Dose and Schedule for Dasatinib in Chronic Myeloid Leukemia: Two Case Reports and Review of the Literature

    Caroline Jamison*, Debra Nelson, Mete Eren, Dron Gauchan, Ryan Ramaekers, Max Norvell, Mehmet Sitki Copur

    Oncology Research, Vol.23, No.1-2, pp. 1-5, 2015, DOI:10.3727/096504015X14452563485986

    Abstract Efficacy and safety of dasatinib in chronic phase (CP) chronic myelogenous leukemia (CML) patients has been well established. Initially approved dose and schedule of 70 mg twice daily has been changed to 100 mg once daily after demonstration of the same efficacy with less toxicity. Some patients require significant dose reductions to enable continued treatment with dasatinib. Even at a dose of 80 mg once daily, several patients may require further dose reductions due to substantial toxicity while maintaining good control of their disease. We report two CP-CML patients achieving and maintaining major molecular responses More >

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