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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 and relapse of disease. The… 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

    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 G2/M arrest due to elevated… More >

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