title: In myelodysplastic syndromes progression to leukemia is directly related to PHA dependency for colony formation and independent of in vitro maturation capacity.
abstract: In an agar-liquid double-layer colony assay in which myeloid leukemia colony-forming cells require the presence of both the lectin PHA and CSF for in vitro proliferation, colony formation of bone marrow cells derived from patients with a myelodysplastic syndrome (MDS) was studied. In five of 14 MDS and all five leukemic transformed MDS cases, colony formation was found to require both PHA and CSF. Three of these five PHA-dependent MDS cases progressed to overt leukemia within 1 year, one progressed from RA to RAEB, and one patient received AML chemotherapy. PHA-dependent colony formation was associated with higher bone marrow blast counts, but not directly to FAB type or cytogenetic abnormalities. In nine other MDS cases only CSF was required for colony formation. In these PHA-independent cases the course of the disease was stable during the observation time (5-17 months). Two types of colonies were observed in this in vitro system: colonies adherent and colonies nonadherent to the agar underlayer. The former consisted of terminally differentiated myeloid cells, and the latter comprised immature cells. This suggests that the percentage of adherent colonies formed in vitro may be used as a measure for the maturation defect in MDS. However, no correlation was found between the percentage of adherent colonies and progression to leukemia of the MDS cases. Our findings suggest that the dependency on PHA for in vitro colony formation of colony-forming cells in MDS is predictive for the progression to leukemia. However, the in vitro differentiation capacity has no apparent prognostic significance.
authors.affiliation: Institute of Hematology, Erasmus University, Rotterdam, The Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: Schipperus
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: R E
authors.initials: RE
authors.lastname: Ploemacher
authors.forename: J
authors.initials: J
authors.lastname: Lindemans
authors.forename: J S
authors.initials: JS
authors.lastname: Voerman
authors.forename: J
authors.initials: J
authors.lastname: Abels
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002448:Cell Adhesion; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications*; D010835:Phytohemagglutinins / Q000494:pharmacology
chemical_list: D010835:Phytohemagglutinins