Abstract
Acute myeloid leukemia is an aggressive disease characterized by clonal proliferation and differentiation into immature hematopoietic cells of dysfunctional myeloid precursors. Accumulating evidence shows that CD34+CD38- leukemia stem cells (LSCs) are responsible for drug resistance, metastasis, and relapse of leukemia. In this study, we found that Nanog, a transcription factor in stem cells, is significantly overexpressed in CD34+ populations from patients with acute myeloid leukemia and in LSCs from leukemia cell lines. Our data demonstrate that the knockdown of Nanog inhibited proliferation and induced cell cycle arrest and cell apoptosis. Moreover, Nanog silencing suppressed the leukemogenesis of LSCs in mice. In addition, we found that these functions of Nanog were regulated by the insulin-like growth factor receptor (IGF1R) signaling pathway. Nanog overexpression rescued the colony formation ability of LSCs treated with picropodophyllin (PPP), an IGF1R inhibitor. By contrast, knockdown of Nanog abolished the effects of IGF2 on the colony formation ability of these LSCs. These findings suggest that the IGF2/IGF1R/Nanog signaling pathway plays a critical role in LSC proliferation.
Highlights
Acute myeloid leukemia is a cancer of myeloid blood cells in the bone marrow (Fialkow et al, 1987)
The expression level of Nanog in leukemia stem cells (LSCs) was analyzed in CD34+ cells isolated from blood samples of patients with acute myeloid leukemia (AML) (Supplementary Table S2) using magnetic-activated cell-sorting (MACS) according to our previous study (Zhang et al, 2015) and in CD34+CD38− LSCs isolated from AML cell lines KG-1a and MOLM13
We found that Nanog shRNAs significantly reduced cell proliferation of KG-1a LSCs and MOLM13 LSCs compared with a control shGFPctrl (Figures 1F,G)
Summary
Acute myeloid leukemia is a cancer of myeloid blood cells in the bone marrow (Fialkow et al, 1987). In the past 40 years, chemotherapy regimens for AML generally included cytarabine in combination with anthracycline (Peloquin et al, 2013). These treatments can often eliminate part of the leukemia cells and extend the life span of the patients, the 5-year survival rate of young patients is still below 40% (Roboz and Guzman, 2009). The homeodomain-containing transcription factor Nanog has received increasing attention because of its pivotal roles in tissue development, stem cell maintenance, and tumor progression (Jeter et al, 2009; Zbinden et al, 2010; Noh et al, 2012). It is not known whether this phenomenon is important to cell growth, increased proliferation is essential to tumor cells (Hanahan and Weinberg, 2011)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
