Granulocyte maturation determines ability to release chromatin NETs and loss of DNA damage response; these properties are absent in immature AML granulocytes

0392658 - BFÚ 2014 RIV NL eng J - Journal Article
Lukášová, Emilie - Kořistek, Z. - Klabusay, M. - Ondřej, Vladan - Grigoryev, S. - Bačíková, Alena - Řezáčová, M. - Falk, Martin - Vávrová, J. - Kohutová, V. - Kozubek, Stanislav
Granulocyte maturation determines ability to release chromatin NETs and loss of DNA damage response; these properties are absent in immature AML granulocytes.
Biochimica Et Biophysica Acta-Molecular Cell Research. Roč. 1833, č. 3 (2013), s. 767-779. ISSN 0167-4889. E-ISSN 1879-2596
R&D Projects: GA ČR(CZ) GAP302/10/1022; GA ČR(CZ) GBP302/12/G157; GA MŠMT(CZ) LD12039; GA ČR(CZ) EE2.3.30.0030
Institutional research plan: CEZ:AV0Z50040702
Institutional support: RVO:68081707
Keywords : NEUTROPHIL EXTRACELLULAR TRAPS * HIGH-RESOLUTION CYTOMETRY * DOUBLE-STRAND BREAKS
Subject RIV: BO - Biophysics
Impact factor: 5.297, year: 2013

Terminally-differentiated cells cease to proliferate and acquire specific sets of expressed genes and functions distinguishing them from less differentiated and cancer cells. Mature granulocytes show lobular structure of cell nuclei with highly condensed chromatin in which HP1 proteins are replaced by MNEI. These structural features of chromatin correspond to low level of gene expression and the loss of some important functions as DNA damage repair, shown in this work and, on the other hand, acquisition of a new specific function consisting in the release of chromatin extracellular traps in response to infection by pathogenic microbes. Granulocytic differentiation is incomplete in myeloid leukemia and is manifested by persistence of lower levels of HP1 gamma and HP1 beta isoforms. This immaturity is accompanied by acquisition of DDR capacity allowing to these incompletely differentiated multi-lobed neutrophils of AML patients to respond to induction of DSB by gamma-irradiation. Immature granulocytes persist frequently in blood of treated AML patients in remission.
Permanent Link: http://hdl.handle.net/11104/0221457