Evaluation of GAB۱ role in pediatric B-cell acute lymphoblastic leukemia

Backgrounds: Acute lymphoblastic leukemia (ALL) is a malignancy in which excessiveproliferation of immature lymphoid cells leads to reduction of normal bone marrow cells. It mostcommonly affects B lymphoblasts where it results in B-ALL and is the most frequent pediatriccancer. A better pathophysiological understanding of this cancer may help create treatmentoptions with less side effects and toxicity. Thus, GAB۱ (Grb۲-associated binder ۱), an adaptorprotein involved in intracellular signal transduction by receptor tyrosine kinases, may be ofspecial interest as it plays an important role in the development of various cancers. However, itsrole in B-ALL is still unclear. Differential gene expression (DGE) and co-expression analysesmay help to explain the role of GAB۱ in this malignancy.Materials and Methods: RNA-seq raw data samples were obtained from ۴ datasets ofBioProject at NCBI database. After pre-processing, data normalization and DGE analysis wereperformed using the DESeq۲ package in R. Then, for gene co-expression and correlationanalysis of GAB۱, WGCNA (Weighted correlation network analysis) package in R andGraphPad Prism were utilized, respectively.Results: GAB۱ was differentially expressed in B-ALL patients compared to the control group(log۲FC= ۴.۹۰, p< ۰.۰۰۰۱). Based on the WGCNA algorithm, PXDN, RN۷SL۱, LEF۱, NRIP۱and UBASH۳B genes had the most significantly related co-expression with GAB۱. Also, theirpositive correlation confirmed in GraphPad Prism.Conclusion: Based on our findings, overexpression of GAB۱ may result in upregulation of genesresponsible for cell growth and proliferation. Indeed, GAB۱ may play an important role inincreasing the proliferation of immature B cells.

کلیدواژه ها:

GAB۱ ، RNA-seq ، Differential expression ، B-ALL