Modulation of the tumor promoting and tumor suppressing roles of ROS in hematopoietic cells of experimental leukemic mice.

Reactive oxygen species (ROS) can cause a lot of pathophysiological consequences, a phenomenon referred to as oxidative stress. With regard to carcinogenesis, ROS is described as a "double-edged sword" due to its condition specific role as a tumor promoter or a tumor suppressor. The current work aims to delineate the mechanistic aspect of this dual role of oxidative stress during hematopoietic malignancy, i.e., leukemia. The study involves N-N' Ethylnitrosourea (ENU) based induction of leukemia in experimental mice followed by the characterization of the disease by investigating the peripheral blood scenario, bone marrow smear study, cytochemistry and histopathology of marrow, flow cytometry based measurement of ROS, and expressional analysis of signaling molecules viz; PCNA, histone-3, CXCR-4, CXCL-12, cyclin-D1, Rb, survivin, and nestin. The result showed that the increased ROS level in leukemic marrow is associated with pathological angiogenesis along with the alteration of CXCR-4/CXCL-12/Cyclin-D axis which was found to be correlated with the hyper-proliferation of the malignant clones. On the other hand, the negation of the tumor suppressive activity of ROS in the hematopoietic compartment of leukemic marrow can be related with the up-regulation of nestin and survivin. The mechanistic study regarding oxidative stress and leukemogenesis may certainly potentiate the development of new anti-leukemic therapeutic strategies.