Sca-1 / c-Kit receptor expression and apoptosis pattern in ENU induced MDS mice

Abstract

The bone marrow is the major site of haemopoiesis in adult human. It contains cells that represent the stages in the development of different types of blood cells e.g. myelocytes, metamyelocytes, erythroblasts, reticulocytes, and other lymphoid progenies etc. Bone marrow failure is primarily the result of a specific failure of bone marrow precursor cells to produce mature cells. N-ethyl N-nitroso urea (ENU) is one of the most potent mutagens that can create an abnormal bone marrow microenvironment by causing defect in haematopoietic stem cell maturation cascade. ENU is easy to administer in mouse, and some probable mutations can be helpful to create models of human diseased conditions like Myelodysplastic syndrome (MDS). MDS is considered as an intravascular bone marrow disorder, a combined structural-functional abnormality wherein the differentiation procedure of the bone marrow stem cell is either incomplete or defective. We assumed that Myelodysplastic syndrome stands in between an inhibitory cellular pattern and a positive overshoot of abnormal differentiations representing an unknown juncture where the mystery of aplasia and leukemia hide back. Instead of using a transgenic mouse model, we attempted to develop an experimentally induced murine model of preleukemia or human MDS like disease model. In doing so ENU has been administered i.p and the animals were examined on thirtieth day and peripheral blood haemogram was documented. Upon registering the appearance of abnormal peripheral blood scenario, the changes in the intravascular bone marrow (BM) architecture, cell surface receptor expression, e.g. Sca-1, c-Kit and the early and late phase apoptic patterns were noted. The results represented an interesting correlation in between bone marrow architecture, early stem cell receptor and apoptic marker expression resembling human MDS.