Analysis of IGFBP7 Expression Level and Its Correlation with Associated Genes in AML Patients.

IGFBP7 (insulin-like growth factor binding protein 7) is a newly-identified protein which can bind with insulin-like growth factors(IGFs), with 45%~65% homology to other IGF binding proteins. Several studies reported that IGFBP7 may be involved in the development of meningioma, breast cancer and prostate cancer, while its correlation with human leukemia had not been reported yet. We have observed an induced expression of IGFBP7 in human leukemia K562 cells which were transfected with and overexpressed RbAp46 gene. Besides, the expression level of WT1, RbAp46 and IGFBP7 was coordinately regulated during the induced differentiation of NB4 acute promyelocytic leukemia cells (data not shown), suggesting a role of IGFBP7 gene in human leukemia.. To investigate the expression level of IGFBP7(previous known as Insulin-like growth factor binding protein related protein 1)in bone marrow (BM) of leukemia patients and its correlation with other leukemia biomarkers, Real-time quantitative reverse transcription polymerase chain reaction (QRT-PCR) method was established for detecting IGFBP7 expression levels in BM of 127 patients with acute leukemia (AL), 24 with chronic myelogenous leukemia in chronic phase (CML-CP), 9 with CML in blast crisis (CML-BC) and 27 with non-leukemias. The M-Estimators of RbAp46_N in 63 patients with newly diagnosed AMLs were higher than those of 27 with ALLs and 27 non-leukemic controls and 10 with AMLs in complete remission(CR)(193.80 v.s 88.84, 81.30 and 67.82, respectively). Although IGFBP7_N was 101.13 in CML-BC and 168.77 in CML-CP, difference between them was not statistically significant. Difference in IGFBP7_N values among CML-BC, AML, ALL and control groups was also not significant. The M-Estimators of IGFBP7_N were lowest in M₄ and highest in M₅ among initial acute leukemia subtypes, and there was statistical differences between M₄ and M₅, and between M₄ and M₂. IGFBP7_N expression level was not correlated to the expression of fusion genes BCR/ABL and AML1/ETO, but it was positively correlated with the expression level of PML/RARαfusion gene, the WT1 and RbAp46 gene. The correlation coefficiency was 0.71, 0.31 and 0.52, respectively. Our results suggested that IGFBP7 might act in WT1 mediating pathway to participate in acute myelocytic leukemias.