title: In vitro suspension culture reactions to 1,25 dihydroxyvitamin D3 in relation to bone marrow morphology and prognosis in patients with myelodysplastic syndromes.
abstract: Thirty-four patients with MDS or AML following MDS were studied with regard to survival, peripheral blood values and bone marrow morphology. The effects of 1,25 dihydroxyvitamin D3 (D3) on differentiation (NBT positivity) and proliferation (3H-thymidine incorporation) were studied in suspension cultures of bone marrow cells. Twelve bone marrow donors served as controls. Normal cells showed spontaneous differentiation in vitro, but only 2/12 were induced to differentiation by D3. Myelodysplastic cells did not differentiate spontaneously, but cells from 18/34 patients differentiated after incubation with D3. Normal cells showed increased proliferation, myelodysplastic cells showed a heterogeneous response and leukemic cells reacted with decreased proliferation after D3 incubation. Poor survival was associated with low platelet counts, high percentage of bone marrow blasts (BM blast %), low spontaneous in vitro proliferation and absence of hypogranulation of myeloid cells. Platelet counts and hypogranulation retained their predictive value in a multi-variate analysis. Progression to AML was predicted by a high BM blast % and low scores for erythroid and total dysplasia. In conclusion, the pattern of in vitro proliferation showed prognostic value while the pattern of vitamin D3-induced differentiation failed to correlate to other parameters. An estimation of bone marrow dysplasia can be used to predict the development of AML. Our results add to the information about the biology of MDS and may be important for the evaluation of therapeutic trials.
authors.affiliation: Department of Medicine, Huddinge University Hospital, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Hellström-Lindberg
authors.forename: K H
authors.initials: KH
authors.lastname: Robèrt
authors.forename: B
authors.initials: B
authors.lastname: Ahnsén
authors.forename: A
authors.initials: A
authors.lastname: Elmhorn-Rosenborg
authors.forename: Y
authors.initials: Y
authors.lastname: Kock
authors.forename: A
authors.initials: A
authors.lastname: Ost
mesh_terms: D000208:Acute Disease; D001853:Bone Marrow / Q000473:pathology*; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000473:pathology*; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000473:pathology*; D011379:Prognosis; D014407:Tumor Cells, Cultured
chemical_list: D002117:Calcitriol