N-Cadherin Aided in Maintaining the Characteristics of Leukemic Stem Cells

Abstract

In our previous study, it has been revealed that N-cadherin+ and leukemic stem cells (LSCs, CD34+/CD38−/CD123+) could be enriched by chemotherapy because of their resistance to chemotherapy. In this study, we found that N-cadherin mRNA was highly expressed in the bone marrow mononuclear cells (BMMNCs) of patients with t(8;21) translocation. To determine the role of N-cadherin in maintaining LSCs self-renewal and stationary properties, colony-forming assay, cell cycle analysis, and engraftment in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice were used to compare N-cadherin+ and N-cadherin− cells. Both leukemic cell lines KG1a and CD34+/CD38− BMMNCs derived from acute myeloid leukemia patients were used, and cells were divided into N-cadherin+ and N-cadherin− fraction after sorting by FACS. The results showed that N-cadherin+ cells had remarkable increased numbers of colonies with cytokines stimulation when compared with the negative control, suggesting a higher proliferative capacity of N-cadherin+ cells with cytokines stimulation. The results also showed that most cells in N-cadherin+ fraction stayed in the G0–G1 stage, indicating the involvement of N-cadherin in maintaining the quiescent state of LSCs in niche. The results of engraftment showed that there was a higher proportion of hCD45+ cells in mice transplanted with N-cadherin+ cells than N-cadherin− cells. In addition, it was obvious that NOD/SCID mice transplanted with N-cadherin+ cells had a shorter lifetime than the negative control, suggesting that LSCs self-renewal capacity resides predominantly in N-cadherin+ fraction. In summary, N-cadherin might play an important role in maintaining the self-renewal and stationary properties of LSCs. Anat Rec, 299:990–998, 2016. © 2016 Wiley Periodicals, Inc.