Jamal Alam, Hassan Dalhat Mahmood, Jahan Sadaf, Choudhry Hani, Imran Khan Mohammad
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah, Saudi Arabia.
Saudi J Biol Sci. 2023 Mar;30(3):103569. doi: 10.1016/j.sjbs.2023.103569. Epub 2023 Jan 25.
Leukemia is a group of diseases characterized by altered growth and differentiation of lymphoid or myeloid progenitors of blood. The existence of specific clusters of cells with stemness-like characteristics like differentiation, self-renewal, detoxification, and resistance to apoptosis in Leukemia makes them difficult to treat. It was recently reported that an oncofetal RNA binding protein, insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), maintains leukemic stem cell properties. BTYNB is an inhibitor of IGF2BP1 that was shown to affect the biological functions of IGF2BP1 however, the effect of BTYNB in Leukemia is not properly established. In this study, we assessed the effect of BTYNB on leukemic cell differentiation and proliferation. We performed cell viability assay to assess the effect of BTYNB in leukemic cells. We then assessed cell morphology of the leukemic cells treated with BTYNB. Further, we conducted an apoptosis assay and cell cycle assay. We found the cell viability of leukemic cells was significantly decreased post treatment with BTYNBs. Further, a noticeable morphological change was observed in BTYNB treated leukemic cells. BTYNB treated leukemic cells showed increased cell death and cell cycle arrest at S-phase. Evidence from the upregulation of and further confirmed apoptosis and cycle arrest. The gene expression of differentiation genes such as , , and were significantly upregulated in BTYNB treated leukemic cells, therefore, confirming cell differentiation. Collectively, our study showed inhibition of IGF2BP1 function using BTYNB promotes differentiation in leukemic cells.
白血病是一组以血液中淋巴细胞或髓细胞祖细胞生长和分化改变为特征的疾病。白血病中存在具有干细胞样特征的特定细胞簇，如分化、自我更新、解毒和抗凋亡能力，这使得它们难以治疗。最近有报道称，一种癌胚RNA结合蛋白，即胰岛素样生长因子2 mRNA结合蛋白1（IGF2BP1），维持白血病干细胞的特性。BTYNB是IGF2BP1的一种抑制剂，已被证明会影响IGF2BP1的生物学功能，然而，BTYNB在白血病中的作用尚未完全明确。在本研究中，我们评估了BTYNB对白血病细胞分化和增殖的影响。我们进行了细胞活力测定，以评估BTYNB对白血病细胞的影响。然后，我们评估了用BTYNB处理的白血病细胞的形态。此外，我们还进行了凋亡测定和细胞周期测定。我们发现，用BTYNB处理后，白血病细胞的活力显著降低。此外，在用BTYNB处理的白血病细胞中观察到了明显的形态变化。用BTYNB处理的白血病细胞显示细胞死亡增加，且细胞周期停滞在S期。 和 的上调证据进一步证实了细胞凋亡和周期停滞。在经BTYNB处理的白血病细胞中， 、 和 等分化基因的基因表达显著上调，因此证实了细胞分化。总的来说，我们的研究表明，使用BTYNB抑制IGF2BP1功能可促进白血病细胞的分化。
