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N‐Cadherin Aided in Maintaining the Characteristics of Leukemic Stem Cells
Author(s) -
Zhi Lei,
Gao Ying,
Yu Chunyan,
Zhang Yi,
Zhang Bo,
Yang Jie,
Yao Zhi
Publication year - 2016
Publication title -
the anatomical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.23345
Subject(s) - cd38 , stem cell , cadherin , cd34 , biology , bone marrow , haematopoiesis , cell sorting , cancer research , progenitor cell , microbiology and biotechnology , immunology , cell , flow cytometry , genetics
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 G 0 –G 1 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.