Ability to downregulate the level of cyclin-dependent kinase inhibitor p27(Kip1) after DNA damage is retained in chronic lymphocytic leukemia cells with functional ATM/p53 signaling pathway

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Authors

KAFKOVA RASKOVA Leona NAVRKALOVÁ Veronika JAROSOVA Marie LOJA Tomáš ČERNÁ Jana KUCEROVA Jana KRIEGOVA Eva PROCHAZKA Vit NOVAK Zdenek SIMKOVA Dana POSPÍŠILOVÁ Šárka DIVOKY Vladimir

Year of publication 2017
Type Article in Periodical
Magazine / Source LEUKEMIA & LYMPHOMA
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://www.tandfonline.com/doi/abs/10.1080/10428194.2016.1187276?journalCode=ilal20
Doi http://dx.doi.org/10.1080/10428194.2016.1187276
Field Oncology and hematology
Keywords PROTEIN EXPRESSION; ATM; APOPTOSIS; SURVIVAL; MYC
Description The activity of the key DNA-damage response (DDR) kinases, ATR and ATM, is largely compromised in chronic lymphocytic leukemia (CLL) cells. While noncycling CLL cells lack ATR protein expression,[1] ATM is commonly targeted for inactivation by genetic abnormalities of the ATM gene.[2] It has been shown that checkpoint pathways, which operate in cycling somatic cells and target Cdk2 kinase activity, are to some extent activated in arrested CLL cells after DNA damage as well;[3] however, the impact of these pathways is questionable, as it could be hampered by predominantly cytoplasmic localization of Cdk2 in CLL cells.[4] Nevertheless, DDR plays a key role in sensitivity of CLL to chemotherapy. Another stress-response kinase, p38 MAP kinase (p38MAPK), was shown to promote CLL cells survival.[5] In multiple cell types, p38MAPK activates different cell cycle checkpoints (mainly through regulation of cyclindependent kinase (Cdk) inhibitors p21Cip1 and p27Kip1), and also ATM/ATR-dependent G2/M checkpoint signaling through MAPKAP kinase-2 activity.[6] While relationship between ATM/p53 and p21Cip1 expression in CLL was studied,[7] the association of ATM kinase activity with the levels of p27Kip1 after DNA damage has not been elucidated in CLL cells.
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