Functional Investigation of CXCR7 Normal and Leukemic Hematopoiesis

Abstract

Bone marrow consists of specific microenvironments called "niches". The osteoblastic niche is responsible for maintenance of hematopoietic stem cells in a more primitive quiescent state, while the vascular niche maintains stem and progenitor cells proliferate and ready to begin the process of differentiation. Recently, the factor SDF-1 (stromal derived factor-1) or CXCL12 was identified as an important chemoattractant factor produced by bone marrow cells. Its action on its receptor CXCR4, expressed by hematopoietic cells, plays major role in the migration, retention and development of hematopoietic progenitors in the bone marrow. Myeloid and lymphoid leukemic cells expressing CXCR4 and take advantage of it to access normally restricted niches spinal progenitor cells, to reside in microenvironments that promote survival and proliferation. Until recently it was believed that only the CXCR4 receptor was SDF-1, but recently it was discovered that the receptor CXCR7 is able to bind to SDF-1. It is expressed in several tumor lines, but in hematopoietic cells and lymphoid its role is still little explored. The acute leukemias are a heterogeneous group of malignant hematopoietic diseases in which the interaction of changes in the bone marrow niche and leukemia cells may determine the course of the disease. Given the paucity of data in the literature, this project aims to verify the role of CXCR7 in normal and leukemic hematopoiesis and contribute to a better understanding of the maintenance of leukemic stem cells in bone marrow patients.