Function and Expression of Insulin-Like Growth Factor–Binding Protein 7 (IGFBP7) Gene in Childhood Acute Myeloid Leukemia

Abstract

Insulin-like growth factor–binding protein 7 (IGFBP7) has been identified as a tumor suppressor in solid tumors. In acute leukemia, the role of IGFBP7 is largely unknown. The authors used quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) to investigate the expression level of IGFBP7 gene in bone marrow (BM) specimen from 66 children with acute myeloid leukemia (AML) at different stages and in 30 nonleukemia patients as control. Furthermore, U937 cells were transfected with siRNA-2 of IGFBP7 (as U937R) for 24 hours. Coculture experiment was performed to explore the impact of IGFBP7 gene in U937 cell adhesion, invasion, and migration in existing ECV304 cells, which mimicked the interaction between AML cells and endothelial cells. IGFBP7 expression at the initial diagnosed stage and relapse of AML was significantly higher than that of control (P < .001). The viable cell percentage in transfected cell was significantly decreased by 42% compared with control groups (P < .01). The percentage for U937R cells adherent to ECV304 cells was significantly lower than the control groups (P < .01). Matrigel study to quantify the invasive potential showed that U937R migrated to the lower chamber were significantly less than those in the parental control groups (P < .01). In summary, IGFBP7 aberrantly overexpressed in majority of AML at diagnosis and upon relapsed, but not at remission stage. IGFBP7 plays a positive contributing role in the interaction between leukemia cells and microenvironment, which may promote the leukemic cells’ adhesion, invasion, and migration.

Keywords :

• acute myeloid leukemia (AML)
• insulin-like growth factor–binding protein 7 (IGFBP7) gene
• leukemic cell line U937
• short interfering RNA (siRNA)