The Effect of Iron on Malignant Lymphoblastic Cells Survival and Its Mechanism

Abstract

Background and Objectives:Anemia is a common complication of chemotherapy. In order to resolve this problem, multiple red blood cell transfusions are administered, leading to iron overload. Given the confirmation of positive correlation between the increased bone marrow iron stores and adverse response to the treatment in the previous study, the effect of iron on the proliferation of acute lymphoblastic leukemia (ALL) cell lines cell lines and its underlying mechanism were investigated in the current study.   Methods:Nalm6 and CCRF-CEM cell lines were selected as representatives of B-ALL and T-ALL Immunophenotypes and were treated with different concentrations of holo-transferrin (1 - 120 µM) and ferric ammonium citrate (FAC) (400 - 25000 µM). The cellular iron uptake was confirmed by AAS test. The cell proliferation and levels of intracellular free radicals (ROS), were evaluated by MTT and flow cytometry, respectively. Statistical analysis was performed using GraphPad prism software by one-way ANOVA test.   Results: The effect of holo-transferrinon cell proliferation was not significant. However, FAC enhanced the proliferation rate of both ALL cell lines over 50%. Evidence showed that iron induced intracellular ROS, so that FAC in the concentration of 400 µM may induce the intracellular ROS over 50% (55.27 6 6.36% vs. 100%, p < 0.001).   Conclusion: Iron can support these cancerous cells by inducing ROS and augmenting leukemic cell proliferation. Therefore, the present study suggests that the volume of the injected blood in ALL patients should be minimized to prevent iron overloa