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

J 2013

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

LUKÁŠOVÁ, E, Zdeněk KOŘÍSTEK, M KLABUSAY, Vladan ONDŘEJ, S GRIGORYEV et. al.

Basic information

Original name

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

Authors

LUKÁŠOVÁ, E, Zdeněk KOŘÍSTEK, M KLABUSAY, Vladan ONDŘEJ, S GRIGORYEV, A BAČÍKOVÁ, M ŘEZÁČOVÁ, Martin FALK, J VÁVROVÁ, V KOHÚTOVÁ and Stanislav KOZUBEK

Edition

Biochimica et biophysica acta : Molecular Cell Research, Amsterdam, Elsevier, 2013, 0167-4889

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 5.297

DOI

http://dx.doi.org/10.1016/j.bbamcr.2012.12.012

Abstract

V originále

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 HP1γ and HP1β 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 γ-irradiation. Immature granulocytes persist frequently in blood of treated AML patients in remission. These granulocytes contrary to mature ones do not release chromatin for NETs after activation with phorbol myristate-12 acetate-13 and do not exert the neutrophil function in immune defence. We suggest therefore the detection of HP1 expression in granulocytes of AML patients as a very sensitive indicator of their maturation and functionality after the treatment. Our results show that the changes in chromatin structure underlie a major transition in functioning of the genome in immature granulocytes. They show further that leukemia stem cells can differentiate ex vivo to mature granulocytes despite carrying the translocation BCR/ABL.

Links

GBP302/12/G157, research and development project

Name: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

Investor: Czech Science Foundation

Citovat

LUKÁŠOVÁ, E, Zdeněk KOŘÍSTEK, M KLABUSAY, Vladan ONDŘEJ, S GRIGORYEV, A BAČÍKOVÁ, M ŘEZÁČOVÁ, Martin FALK, J VÁVROVÁ, V KOHÚTOVÁ and Stanislav KOZUBEK. Granulocyte maturation determines ability to release chromatin NETs and loss of DNA damageresponse; these properties are absent in immature AML granulocytes. Biochimica et biophysica acta : Molecular Cell Research. Amsterdam: Elsevier, 2013, vol. 1833, No 3, p. 767-779. ISSN 0167-4889. Available from: https://dx.doi.org/10.1016/j.bbamcr.2012.12.012.

@article{1594222,
   author = {Lukášová, E and Kořístek, Zdeněk and Klabusay, M and Ondřej, Vladan and Grigoryev, S and Bačíková, A and Řezáčová, M and Falk, Martin and Vávrová, J and Kohútová, V and Kozubek, Stanislav},
   article_location = {Amsterdam},
   article_number = {3},
   doi = {http://dx.doi.org/10.1016/j.bbamcr.2012.12.012},
   language = {eng},
   issn = {0167-4889},
   journal = {Biochimica et biophysica acta : Molecular Cell Research},
   title = {Granulocyte maturation determines ability to release chromatin NETs and loss of DNA damageresponse; these properties are absent in immature AML granulocytes},
   volume = {1833},
   year = {2013}
}

TY  - JOUR
ID  - 1594222
AU  - Lukášová, E - Kořístek, Zdeněk - Klabusay, M - Ondřej, Vladan - Grigoryev, S - Bačíková, A - Řezáčová, M - Falk, Martin - Vávrová, J - Kohútová, V - Kozubek, Stanislav
PY  - 2013
TI  - Granulocyte maturation determines ability to release chromatin NETs and loss of DNA damageresponse; these properties are absent in immature AML granulocytes
JF  - Biochimica et biophysica acta : Molecular Cell Research
VL  - 1833
IS  - 3
SP  - 767-779
EP  - 767-779
PB  - Elsevier
SN  - 01674889
N2  - 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 HP1γ and HP1β 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 γ-irradiation. Immature granulocytes persist frequently in blood of treated AML patients in remission. These granulocytes contrary to mature ones do not release chromatin for NETs after activation with phorbol myristate-12 acetate-13 and do not exert the neutrophil function in immune defence. We suggest therefore the detection of HP1 expression in granulocytes of AML patients as a very sensitive indicator of their maturation and functionality after the treatment. Our results show that the changes in chromatin structure underlie a major transition in functioning of the genome in immature granulocytes. They show further that leukemia stem cells can differentiate ex vivo to mature granulocytes despite carrying the translocation BCR/ABL.
ER  -

LUKÁŠOVÁ, E, Zdeněk KOŘÍSTEK, M KLABUSAY, Vladan ONDŘEJ, S GRIGORYEV, A BAČÍKOVÁ, M ŘEZÁČOVÁ, Martin FALK, J VÁVROVÁ, V KOHÚTOVÁ and Stanislav KOZUBEK. Granulocyte maturation determines ability to release chromatin NETs and loss of DNA damageresponse; these properties are absent in immature AML granulocytes. \textit{Biochimica et biophysica acta : Molecular Cell Research}. Amsterdam: Elsevier, 2013, vol.~1833, No~3, p.~767-779. ISSN~0167-4889. Available from: https://dx.doi.org/10.1016/j.bbamcr.2012.12.012.

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