RESPONSE OF MYELODYSPLASTIC SYNDROME BONE-MARROW CELLS TO MULTIPLE CYTOKINE STIMULATION IN LIQUID CULTURES - AN IN-SITU HYBRIDIZATION STUDY

Background and Objective. Myelodysplastic syndrome progenitor cells ca n be grown and expanded in long term bone marrow liquid cultures in th e presence of multiple cytokines. In this study we investigated the pa ttern of differentiation and response to growth factors in six cases o f myelodysplastic syndrome (MDS) with well-defined cytogenetic abnorma lities by means of conventional cytogenetics and fluorescence in situ hybridization (FISH). Methods. Bone marrow cells were grown in stroma- free liquid cultures in the presence of SCF, IL-3, IL-6 and GM-CSF. Re sults. In three cases a CFU-GM expansion comparable to normal controls was observed, together with a decrease or increase of cells with abno rmal karyotype. Two cases showed no response to growth factor stimulat ion, morphological signs of terminal myeloid differentiation and incre ase (one case) or decrease (one case) in the percentage of abnormal FI SH signals along the cultures. In one additional case, while CFU-C exp ansion was present, clearcut leukemic transformation was observed in t he culture, together with a sharp decrease in the percentage of abnorm al FISH signals, indicating a leukemic transformation of MDS progenito r cells with a normal karyotype. Interpretation and Conclusions. Our d ata indicate that FISH analysis is generally a poor indicator of clona lity in MDS; nevertheless, determining the kinetics of cytogenetically abnormal clones in liquid bone marrow cultures may provide insight as to the growth abnormalities of MDS progenitor cells and may be useful prior to in vivo growth factor administration. (C) 1997, Ferrata Stor ti Foundation.