Mast cell growth factor (c-kit ligand) restores growth of multipotent progenitors in myelodysplastic syndrome

Betty Glinsmann-Gibson, Catherine Spier, Monika Baier, Raymond Taetle, Virginia C. Broudy, Alan F. List

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

In vitro growth of primitive hematopoietic progenitors is severely impaired in the myelodysplastic syndromes (MDS). To determine if the c-kit ligand mast cell growth factor (MGF) can improve progenitor growth in MDS, we evaluated in vitro responsiveness of bone marrow progenitors from 25 patients to MGF and/or GM-CSF, interleukin-3 (IL-3) and PIXY 321, and examined the relationship between progenitor response and cellular expression of the c-kit receptor. MGF and erythropoietin gave rise to macroscopic colonies and dose-dependently increased CFU-GEMM and BFU-E up to 27-fold in 15 (60%) and 20 (80%) patients, respectively. Among 17 patients with absent growth in lymphocyte-conditioned media, MGF stimulated CFU-GEMM recovery in 59%, compared to 23% with PIXY 321, 12% with IL-3 and 8% with GM-CSF. Cytokine combinations did not augment recovery of erythropoietin-dependent progenitors above that achieved with MGF alone. MGF and/or IL-3 were comparatively weak stimulants of CFU-GM formation, whereas GM-CSF and PIXY in combination with MGF increased colony number 2- to 15-fold in 60 and 70% of patients, respectively, while preserving maturation competence as evidenced by colony composition and increased colony/cluster ratio. The stimulatory effects of MGF were observed in all morphologic categories of MDS except chronic myelomonocytic leukemia. A mononuclear cell population expressing the c-kit receptor was identified by flow cytometry in 57% of cases. Neither SR-1 reactivity nor cytogenetic pattern predicted progenitor response to MGF. These data indicate that MGF improves the colony-forming capacity of hematopoietic progenitors in MDS and is a potent co-stimulant of multipotent and committed progenitor recovery. The heterogeneity in MGF responsiveness implies an intrinsic defect in growth regulation not explained by cellular loss of c-kit display.

Original languageEnglish (US)
Pages (from-to)827-832
Number of pages6
JournalLeukemia
Volume8
Issue number5
StatePublished - May 1994

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Mast cell growth factor (c-kit ligand) restores growth of multipotent progenitors in myelodysplastic syndrome'. Together they form a unique fingerprint.

  • Cite this

    Glinsmann-Gibson, B., Spier, C., Baier, M., Taetle, R., Broudy, V. C., & List, A. F. (1994). Mast cell growth factor (c-kit ligand) restores growth of multipotent progenitors in myelodysplastic syndrome. Leukemia, 8(5), 827-832.