title: Megakaryocytic growth in patients with refractory anemia is suppressed by treatment with interferon alpha.
abstract: IFN alpha alone or in combination with retinoids or haematopoietic growth factors has been used to treat patients with early MDS because of its properties as a differentiation inducing agent. We investigated whether treatment of patients with refractory anemia (RA) with IFN alpha (1.5x10(6) IU twice a week) and intermittent all-trans retinoic acid (ATRA, 25 mg/m2/d) influences in-vitro megakaryocytic (MK) proliferation and differentiation stimulated by PEG-rHuMGDF. Low-density non-adherent bone marrow (BM) cells from 8 patients with RA were assayed prior to any treatment other than supportive and after a period of 6 months of treatment. MK development was assayed in suspension cultures in the presence of PEG-rHuMGDF and SCF for 7 d using morphological criteria and flow cytometric analysis of CD42b (GP1b) positive cells. BM-cells from 10 healthy individuals served as control. Following stimulation with PEG-rHuMGDF 23+/-7% and 16+/-4% of control cells were CD42b positive after 5 and 7 d of cultures, respectively. In cultures of cells from MDS patients prior to treatment 8+/-2% and 7+/-3% of cells were CD42b+ on days 5 and 7. In the course of IFN alpha treatment cultures of all BM samples from these MDS patients revealed a significant reduction of MK precursor cells (3+/-2%, CD42b+, p=0.03 and 0.04). In conclusion, treatment with TFN alpha and ATRA did not result in improved megakaryocytopoiesis as assessed by in-vitro cultures. On the contrary, low-dose IFN alpha appears to suppress cell proliferation as well as MK development.
authors.affiliation: Department of Haematology, Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany. W.K.Hofmann@em.uni-frankfurt.de
authors.forename: W K
authors.initials: WK
authors.lastname: Hofmann
authors.forename: U
authors.initials: U
authors.lastname: Kalina
authors.forename: G
authors.initials: G
authors.lastname: Seipelt
authors.forename: K
authors.initials: K
authors.lastname: Hoffmann
authors.forename: S
authors.initials: S
authors.lastname: Wagner
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D051927:CD24 Antigen; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects* / Q000473:pathology*; D008562:Membrane Glycoproteins; D008875:Middle Aged; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D051927:CD24 Antigen; C497889:CD24 protein, human; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D014212:Tretinoin