FLT3 Ligand Inhibits Apoptosis and Promotes Survival of Myeloid Leukemia Cell Lines

Abstract

Growth factors (cytokines) are considered to be key regulators of hematopoiesis, in particular by stimulating growth or maintaining viability mainly of progenitor cells, but also of more mature cells. We examined cytokine-stimulated survival of constitutively growth factor-dependent acute myeloid leukemia (AML)-derived cell lines. The cells from the four cell lines MUTZ-2 (AML M2-derived), OCI/AML5 (AML M4), TF-I (AML M6) and UT-7 (AML M7) undergo apoptosis quickly in the absence of cytokines in serum-free medium: half-lives of serum-and factor-deprived cells ranged from 14 to 64 h. Here, we analyzed the survival-promoting and apoptosis-inhibiting properties of FLT3 ligand (FL) using the viable cell count as an indicator of programmed cell death. The receptor for FL belongs to the class III family of receptor tyrosine kinases which also includes c-kit, the receptor for stem cell factor (SCF). FL extended the survival of cell lines MUTZ-2 and OCI/AML5, but was not effective for cell lines TF-I and UT-7. In OCI/AML5, the action of FL was evident both in first promoting survival and then stimulating proliferation slightly. In MUTZ-2, depending on the concentration used, FL extended survival by 64–135% compared with control cells. SCF alone prolonged cell survival of MUTZ-2 as well, however, FL and the combination of FL+SCF was significantly more active. Thus, FL alone, and in combination with SCF, was active in promoting survival and proliferation of human AML cells in vitro.

Key Words:

• Cytokines
• FLT 3 Ligand
• SCF
• Leukemia
• Cell Lines
• Apoptosis