Analysis of bone morrow mesenchymal cells from patients with acute myeloid leukemia and from healthy subjects in an assay of coculture with leukemic blats

Abstract

An essential microenvironment maintains the properties of auto regulation and auto differentiation of HSCs and differentiated progenitors in BM. One of the main elements of the microenvironment are MSCs, they compose the medullar stromal tissue and are extremely relevant in the process of hematopoiesis and immunologic regulation. There is scientific data describing three distinct populations of HSCs exposed to co-culture with MSCs: those in supernatant (Group A), those adhering to the surface of MSCs (Group B) and those beneath the MSCs (Group C). Besides it were observed that MSCs perform the transfer of ROS trough gap junctions to HSCs in healthy subjects. The ROS concentration in HSCs was related to a higher mobility and motility of these cells. ROS production was associated with increase of disease recurrence in AML patients, suggesting to be an important prognosis factor. On the other hand, Ras gene mutations related to constitutive activation of protein induce an increase activation of NOX2 and, consequently, elevate ROS production in CD34+ cells, thereby, they contribute to develop the leukemic phenotype. Furthermore, it was observed the production of PGE2 by COX2 of MSCs. When it was secreted in the extracellular environment contiguous with HSCs, these cells reduce the levels of intracellular ROS. In this study, we try to demonstrate the hole of MSCs favoring the surviving of malignancy cells through the reduction of the cellular damage, induction of quiescence and/or reduction of apoptosis induced by ROS. (AU)