Kumar Himansu, Tichkule Swapnil, Raj Utkarsh, Gupta Saurabh, Srivastava Swati, Varadwaj Pritish Kumar
Indian Institute of Information Technology, Allahabad, 211012, India.
3 Biotech. 2016 Jun;6(1):40. doi: 10.1007/s13205-015-0357-7. Epub 2016 Jan 27.
Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disorder which proliferates due to abnormal growth of basophil cells. Several proangiogenic molecules have been reported to be associated in CML progression, including the hepatocyte growth factor (HGF). However, detail mechanism about the cellular distribution and function of HGF in CML is yet to be revealed. The proliferation of hematopoietic cells are regulated by some of the growth factors like interleukin 3 (IL-3), IL-6, erythropoietin, thrombopoietin, etc. In this study IL-6 pathways have been taken into consideration which induces JAK/STAT and MAPK pathways to decipher the CML progression stages. An attempt has been made to model these pathways with the help of ordinary differential equations (ODEs) and estimating unknown parameters through fminsearch optimization algorithm. Some of the specific component like STAT3, of the pathway has been analyzed in detail and their role in CML progression has been elucidated. The roles of STAT3 inhibitors into the treatment of CML have been thoroughly studied and optimum concentration of the inhibitors have been predicted.
慢性粒细胞白血病（CML）是一种造血干细胞疾病，由于嗜碱性粒细胞的异常生长而增殖。据报道，几种促血管生成分子与CML的进展有关，包括肝细胞生长因子（HGF）。然而，HGF在CML中的细胞分布和功能的详细机制尚待揭示。造血细胞的增殖受一些生长因子的调节，如白细胞介素3（IL-3）、IL-6、促红细胞生成素、血小板生成素等。在本研究中，考虑了诱导JAK/STAT和MAPK途径的IL-6途径，以解读CML的进展阶段。已尝试借助常微分方程（ODE）对这些途径进行建模，并通过fminsearch优化算法估计未知参数。对该途径的一些特定成分，如STAT3进行了详细分析，并阐明了它们在CML进展中的作用。已对STAT3抑制剂在CML治疗中的作用进行了深入研究，并预测了抑制剂的最佳浓度。
