An integrated approach for the understanding of association of JAK1 mutations in Chronic Myeloid Leukemia

JAKs are the class of protein tyrosine kinases that connect with intracellular cytokine receptors and become active when the extra-cellular ligand-receptor interaction is trans-phosphorylated. By assisting tumor cells in squeezing through tiny capillaries and tissues and spreading to different regions of the body, it plays crucial functions in JAK/STAT signaling, particularly in immunity, cell proliferation, apoptosis, and tumor metastasis. Mutations in the JAK1 gene have already been connected to a variety of hema-tological cancers and other cancer types. The onset and course of chronic myeloid leukemia (CML) may be linked to certain muta-tions in the JAK1 gene. The previous findings make it more interesting to study the association of the JAK1 gene with the Philadel-phia chromosome (Ph. Ch.) in CML disease since it may become a way to suppress by gene-targeting therapies. There exists knowledge gap regarding the effect of JAK mutations in CML patients overall/disease-free/event-free survival rates which also further reflects the importance of our study especially in Saudi Arabia. Thus, we have potentially focused on JAK1 mutations in CML patients by using sequencing techniques for the potential exons and also by using in-silico approach by using publicly avail-able datasets. Here, we have explored the association of JAK1 with potential genes and the critical biological functions by using network-level understanding and the putative herbal drugs for targeting purpose. Our results show potential difference in the se-lected patients in terms of the sequences and JAK1 may act as a master regulator of critical biological functions and their compo-nents. Furthermore, the integrated approach leads to the conclusion that ATM, JAK1, TP53, KRAS, and BRAF as the most critical genes and KRAS and TP53 show maximum binding affinity (-8.41 kcal/mol (quercetin with KRAS), -8.17 kcal/mol (resveratrol with KRAS), -8.08 kcal/mol (apigenin with TP53).