Defect of Stromal Microenvironment in Long Term Bone Marrow Cultures of Patients with Acute and Chronic Myelogenous Leukemias

Abstract

Inhibition of normal hemopoiesis is a regular finding in acute (AML) and chronic (CML) myelogenous leukemias and functional abnormalities of the hemopoietic microenvironment may be involved in this regard. In order to evaluate this possibility we studied the formation of adherent stromal cell layers (ASCL) in long term bone marrow cultures (LTBMC) of 7 patients with CML and 7 patients with AML and examined the ability of these ASCLs to support hemopoiesis after irradiation and a second inoculation of bone marrow cells. The formation of ASCLs was significantly impaired in CML and AML. These CML patients and 3 AML patients did not form typical ASCLs and the cellularity of these layers was greatly reduced. Colony forming unit granulocyte-macrophage (CFU-GM) production from bone marrow cells seeded on normal irradiated ASCLs peaked at week 3 and then gradually decreased by week 8. In CML and AML cocultures CFU-GM numbers decreased rapidly to zero by weeks 4-6 and did not differ Significantly from the control cultures which did not contain preestablished ASCLs beginning from week 3. It is suggested that there may be a functional microenvironmental defect in CML and AML that may play a role in the pathogenesis of inhibition of normal hemopoiesis in these diseases.

Key Words:

• microenvironment
• leukemia
• marrow culture
• stroma
• hemopoiesis
• CFU-GM