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The death‐associated protein kinase 2 is up‐regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells
Author(s) -
Rizzi Mattia,
Tschan Mario P.,
Britschgi Christian,
Britschgi Adrian,
Hügli Barbara,
Grob Tobias J.,
Leupin Nicolas,
Mueller Beatrice U.,
Simon HansUwe,
Ziemiecki Andrew,
Torbett Bruce E.,
Fey Martin F.,
Tobler Andreas
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0606400
Subject(s) - biology , myeloid , myelopoiesis , myeloid leukemia , cancer research , cd34 , cellular differentiation , integrin alpha m , microbiology and biotechnology , haematopoiesis , immunology , stem cell , flow cytometry , gene , biochemistry
The death‐associated protein kinase 2 (DAPK2) belongs to a family of Ca 2+ /calmodulin‐regulated serine/threonine kinases involved in apoptosis. During investigation of candidate genes operative in granulopoiesis, we identified DAPK2 as highly expressed. Subsequent investigations demonstrated particularly high DAPK2 expression in normal granulocytes compared with monocytes/macrophages and CD34 + progenitor cells. Moreover, significantly increased DAPK2 mRNA levels were seen when cord blood CD34 + cells were induced to differentiate toward neutrophils in tissue culture. In addition, all‐trans retinoic acid (ATRA)‐induced neutrophil differentiation of two leukemic cell lines, NB4 and U937, revealed significantly higher DAPK2 mRNA expression paralleled by protein induction. In contrast, during differentiation of CD34 + and U937 cells toward monocytes/macrophages, DAPK2 mRNA levels remained low. In primary leukemia, low expression of DAPK2 was seen in acute myeloid leukemia samples, whereas chronic myeloid leukemia samples in chronic phase showed intermediate expression levels. Lentiviral vector‐mediated expression of DAPK2 in NB4 cells enhanced, whereas small interfering RNA‐mediated DAPK2 knockdown reduced ATRA‐induced granulocytic differentiation, as evidenced by morphology and neutrophil stage‐specific maturation genes, such as CD11b, G‐CSF receptor, C/EBPε, and lactoferrin. In summary, our findings implicate a role for DAPK2 in granulocyte maturation.

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