The Role Of IGF-IR In The Proliferation Of Clonal Cells From Myelodysplastic Syndromes

To investigate the role of type 1 insulin-like growth factor receptor(IGF-IR)in proliferation of clonal cells in myelodysplastic syndromes(MDS),the expression level of IGF-IR in different bone marrow cell fractions of MDS and its relationship with proliferation of clonal cells for the potential of using IGF-IR as a marker of clonal cells were analyzed firstly.And then purifying bone marrow clonal cells from patients with MDS via IGF-IR using flow cytometry was studied.At last,the IGF-IR expression was down regulated by RNA interference(RNAi)and the kinase activities of IGF-IR were inhibited by the IGF-IR specific inhibitor picropodophyllin(PPP)in vitro.The cell proliferation,cell apoptosis and cell cycle of MDS cell lines or CD34~+cells from MDS patients were analyzed.The changes of different signaling pathway genes and proteins were detected by gene expression profile chip and flow cytometry.The results showed that the average percentage of CD34~+cells with IGF-IR expression from MDS patients increased progressively.The relationship of IGF-IR with the proliferation of clonal cells was proved by PPP interference in vitro.The percentage of clonal cells significantly increased after IGF-IR sorting.So IGF-IR can be used as a marker for MDS bone marrow clonal cells.IGF-IR could promote cell proliferation,inhibit cell apoptosis and induce malignant transformation to acute leukemia possibly through the PI3K/AKT,ERK/MAPK and Jak/STAT3 pathways in MDS.The down-regulation of IGF-IR could inhibit cell proliferation,promote cell apoptosis and block the cell cycle at the G2/M phase in MDS.Taken together,using flow cytometry for positive IGF-IR sorting may effectively purify MDS clonal cells,which can be useful to the experimental research of clonal cells.IGF-IR could regulate the proliferation of MDS clonal cells through multiple signaling transduction pathways,and it would be of some significance to predict transformation to acute leukemia through monitoring the IGF-IR expression of patients by flow cytometry.