Glia maturation factor gamma, is a novel diagnostic marker of leukemia, has TAL1 binding sites in its promoter

Abstract

Glia maturation factor gamma (GMFG) overexpression increases T-cell migration and adhesion. Its high expression in colorectal and ovarian cancer is associated with chemoresistance and adverse prognosis. However, it remains elusive if GMFG plays a role in the development and progression of leukemia. Tissue invasion in leukemia has long been known as the reason for disease progression as leukemic cells accumulates in bone marrow, spleen and lymph nodes. This tissue invasion requires cell motility and migration. The aim of the present study was to find any association of GMFG expression with leukemia and its potential to be a diagnostic marker. For this purpose, we have carried out expression profiling of GMFG among a cohort of leukemia patients. Liquid biopsies were collected and subjected to GMFG expression analysis. We found that GMFG expression was significantly elevated among leukemia patients of all age groups relative to their age match controls. Further promoter analysis of GMFG reveals binding sites for T-cell Acute Lymphocytic Leukemia 1 (TAL1) and associated transcription factors. TAL1 is master transcription factor which, in coordination with other factors like GATA-binding protein 1 (GATA-1) and LIM domain only 2 (LMO2), regulates gene expression in T-cell leukemia. The induced TAL1 expression coincides with upregulated GMFG expression. Together these data suggest that TAL1 may bind to GMFG promoter to increase its expression. GMFG may play a crucial role in the motility of leukemic cells and facilitates their tissue invasion which leads to therapy resistance.