DEFECT OF STROMAL MICROENVIRONMENT IN LONG-TERM BONE-MARROW CULTURES OF PATIENTS WITH ACUTE AND CHRONIC MYELOGENOUS LEUKEMIAS

Inhibition of normal hemopoiesis is a regular finding in acute (AML) a nd chronic (CML) myelogenous leukemias and functional abnormalities of the hemopoietic microenvironment may be involved in this regard. In o rder 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 abilit y of these ASCLs to support hemopoiesis after irradiation and a second inoculation of bone marrow cells. The formation of ASCLs was signific antly impaired in CML and AML. These CML patients and 3 AML patients d id not form typical ASCLs and the cellularity of these layers was grea tly reduced, Colony forming unit granulocyte-macrophage (CFU-GM) produ ction from bone marrow cells seeded on normal irradiated ASCLs peaked at week 3 and then gradually decreased by week 8. In CML and AML cocul tures CFU-GM numbers decreased rapidly to zero by weeks 4-6 and did no t differ significantly from the control cultures which did not contain preestablished ASCLs beginning from week 3. It is suggested that ther e may be a functional microenvironmental defect in CML and AML that ma y play a role in the pathogenesis of inhibition of normal hemopoiesis in these diseases.