The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells

Rizzi, Mattia; Tschan, Mario P; Britschgi, Christian; Britschgi, Adrian; Hügli, Barbara; Grob, Tobias J; Leupin, Nicolas; Mueller, Beatrice U; Simon, Hans-Uwe; Ziemiecki, Andrew; Torbett, Bruce E; Fey, Martin F; Tobler, Andreas (2007). The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells. Journal of leukocyte biology, 81(6), pp. 1599-608. Bethesda, Md.: Society for Leukocyte Biology 10.1189/jlb.0606400

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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/EBPepsilon, and lactoferrin. In summary, our findings implicate a role for DAPK2 in granulocyte maturation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory

UniBE Contributor:

Rizzi, Mattia; Müller, Beatrice Ursula; Simon, Hans-Uwe; Fey, Martin and Tobler, Andreas

ISSN:

0741-5400

ISBN:

17347302

Publisher:

Society for Leukocyte Biology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:53

Last Modified:

04 May 2014 23:15

Publisher DOI:

10.1189/jlb.0606400

PubMed ID:

17347302

Web of Science ID:

000246988600027

URI:

https://boris.unibe.ch/id/eprint/22399 (FactScience: 34526)

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