Abnormal regulation of granulopoiesis by bone marrow fibroblasts in leukemia

Effects of human bone marrow fibroblasts (BMF) on the differentiation of human colony forming units in culture (CFU-C) were investigated in five normal adults, 10 patients with acute leukemia (AL) at the time of diagnosis, five patients with AL at complete remission (CR) and six patients with chronic myelogenous leukemia (CML). To determine the effects of BMF on granulopoiesis, normal bone marrow cells were cultured in agar medium on BMF liquid-phase cultures, and the numbers of CFU-C were counted. BMF from either normal subjects, AL at the time of complete remission (CR) or CML enhanced the growth of CFU-C in a few spontaneous CFU-C groups (less than 3 colonies/10(5) cells), whereas BMF obtained from AL at the time of diagnosis failed to enhance the growth. In contrast, BMF from either normal subjects, AL at the time of diagnosis and CR, or CML inhibited the growth of CFU-C in many spontaneous CFU-C groups (greater than 10 colonies/10(5) cells). BMF from AL at the time of diagnosis showed significantly higher inhibitory effect than those from normal subjects (p less than 0.01). When giant cell tumor-conditioned medium was used as a source of colony stimulating factor, 26 BMF in total from various subjects inhibited the growth of CFU-C except for four cases (two normal subjects and two AL patients at CR). The degree of inhibition of CFU-C growth by BMF from AL at the time of diagnosis was significantly higher than in normal subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)