PERTURBATION IN THE ABILITY OF BONE-MARROW STROMA FROM PATIENTS WITH ACUTE MYELOID-LEUKEMIA BUT NOT CHRONIC MYELOID-LEUKEMIA TO SUPPORT NORMAL EARLY HEMATOPOIETIC PROGENITOR

The ability of bone marrow (BM) stroma derived from patients with acut e myeloid leukemia (AML) or chronic myeloid leukemia (CML) to support normal hematopoiesis was investigated using a two-stage long-term bone marrow culture (LTBMC) procedure. Of particular interest was whether leukemia-derived stroma were capable of supporting the very immature, uncommitted hematopoietic progenitor cells (HPC) which are considered to have a higher dependence and association with the BM stroma than th e more mature committed HPC. Confluent stromal layers were recharged w ith selected populations of normal HPC enriched for the CD34(+)CD38(-) cells (immature, uncommitted HPC) or the CD34(+)CD38(+) cells (mature , committed HPC). The weekly output of clonable granulocyte-macrophage progenitor cells (CFU-GM) was used as an indicator of the hematopoiet ic-supporting ability of the cultures. Stromal layers derived from 5/7 patients newly diagnosed with AML, showed significantly depressed abi lity to support the CD34(+)CD38(-) cells compared to stroma derived fr om normal donors. The supporting function of the AML-derived stroma fo r the more mature CD34(+)CD38(+) cells was similar to that of the norm al stroma (3/3 cases). Stromal layers derived from patients with chron ic-phase CML showed normal or enhanced supporting function for the CD3 4(+)CD38(-) cells (5/6 cases), and likewise for the CD34(+)CD38(-) cel ls (3/3 cases). This study revealed a selective defect in the ability of BM stroma from patients with AML to support the maturation of norma l early uncommitted HPC, represented by the CD34(+)CD38(-) cells, whil st the ability to support the committed CD34(+)CD38(+) cells was not a ffected. This suggests that the BM microenvironment may be implicated in the disease mechanism of AML. It does not, however, appear to be as clearly implicated in chronic-phase CML. (C) 1997 Elsevier Science Lt d.