Cytarabine and EIP co-administration synergistically reduces viability of acute lymphoblastic leukemia cells with high ERG expression

Abstract

The E26 transformation sequence-related gene ERG encodes a transcription factor involved in normal hematopoiesis, and its expression is abnormal in leukemia. Especially in a type of acute lymphoblastic leukemia (ALL) that is refractory and easy to relapse, the expression of ERG protein is abnormally increased. Chemotherapy can alleviate the condition of ALL, but the location and survival mechanism of the remaining ALL cells after chemotherapy are still not fully understood. It is becoming increasingly clear that the interaction between leukemia cells and their microenvironment plays an important role in the acquisition of drug resistance mutations and disease recurrence. We selected an acute lymphocytic leukemia cell line with high ERG expression, and studied the synergistic effect of chemotherapeutics and small molecule peptides through cell proliferation, apoptosis, and cell cycle experiments; At the same time, we inoculated acute lymphocytic leukemia cells with high ERG expression into mice with severe immunodeficiency to simulate human ALL and investigated (i) the effects of co-administration on the nesting and invasion of leukemia cells and (ii) the effects of the small molecule peptide drug EIP, which targets ERG, on the sensitivity of ALL chemotherapy and the underlying mechanisms.Ara-c and EIP synergistically reduces viability of ALL cells with high ERG expression may be achieved by promoting their apoptosis and inhibiting their nesting.