Effect of stem cell factor on leukemic progenitor cell growth and sensitivity to cytosine-arabinoside

Leuk Res. 1996 Nov-Dec;20(11-12):915-23. doi: 10.1016/s0145-2126(96)00058-6.

Abstract

Recruitment of quiescent, clonogenic blasts from patients with acute myeloid leukemia (AML) by hematopoietic growth factors (HGFs) may improve the cytotoxic effects of cell-cycle-specific drugs like cytosine-arabinoside (Ara-C). Using the culture methods described by Nara and McCulloch and making a distinction between self-renewing and post-deterministic mitoses, we analyzed the effects of stem cell factor (SCF), a growth factor acting on early hematopoietic progenitor and stem cells. First, we demonstrated that SCF, used in combination with other HGFs included in fetal calf serum (FCS) and/or in 5637 cell line supernatant (5637-CM), stimulated both colony formation and self-renewal of blast progenitors from 10 patients, unlike SCF alone. We tested the effects of SCF on the recruitment of cells in the S-phase by using a bromodeoxyuridine/DNA (BrdUrd/DNA) staining method in flow cytometry (FCM). We showed that SCF stimulated proliferation of AML cells significantly in 9/18 patients with AML. Second, we tested the influence of SCF on the sensitivity to Ara-C of self-renewing leukemic cells from 18 patients with AML. We showed that SCF was efficient in increasing the toxicity of Ara-C on the self-renewing blast progenitors, especially with high concentrations of Ara-C. However, a large patient-to-patient heterogeneity was found and the activity of SCF was not correlated with its effect on the cell cycle. These data indicate that SCF can enhance sensitivity to Ara-C of some leukemic cells with self-renewing capacity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Cattle
  • Cell Cycle / drug effects
  • Culture Media / pharmacology
  • Culture Media, Serum-Free / pharmacology
  • Cytarabine / pharmacology*
  • DNA Replication / drug effects
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Female
  • Fetal Blood / chemistry
  • Flow Cytometry
  • Hematopoietic Cell Growth Factors / isolation & purification
  • Hematopoietic Cell Growth Factors / pharmacology
  • Humans
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology*
  • Male
  • Methylcellulose
  • Middle Aged
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Recombinant Proteins / pharmacology
  • Stem Cell Factor / pharmacology*
  • Suspensions
  • Tumor Stem Cell Assay

Substances

  • Antimetabolites, Antineoplastic
  • Culture Media
  • Culture Media, Serum-Free
  • Hematopoietic Cell Growth Factors
  • Recombinant Proteins
  • Stem Cell Factor
  • Suspensions
  • Cytarabine
  • Methylcellulose