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Potential role of A...
Potential role of AKT/mTOR signalling proteins in hairy cell leukaemia: association with BRAF/ERK activation and clinical outcome
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Lakiotaki, E (author)
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Levidou, G (author)
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Angelopoulou, MK (author)
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Adamopoulos, C (author)
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Pangalis, G (author)
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- Rassidakis, G (author)
- Karolinska Institutet
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Vassilakopoulos, T (author)
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Gainaru, G (author)
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Flevari, P (author)
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Sachanas, S (author)
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Saetta, AA (author)
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Sepsa, A (author)
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Moschogiannis, M (author)
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Kalpadakis, C (author)
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- Tsesmetzis, N (author)
- Karolinska Institutet
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Milionis, V (author)
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Chatziandreou, I (author)
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Thymara, I (author)
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Panayiotidis, P (author)
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Dimopoulou, M (author)
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Plata, E (author)
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Konstantopoulos, K (author)
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Patsouris, E (author)
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Piperi, C (author)
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Korkolopoulou, P (author)
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(creator_code:org_t)
- 2016-02-19
- 2016
- English.
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 21252-
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https://www.nature.c...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- The potential role of AKT/mTOR signalling proteins and its association with the Raf-MEK-ERK pathway was investigated in hairy cell leukaemia (HCL). BRAFV600E expression and activated forms of AKT, mTOR, ERK1/2, p70S6k and 4E-BP1 were immunohistochemically assessed in 77 BM biopsies of HCL patients and correlated with clinicopathological and BM microvascular characteristics, as well as with c-Caspase-3 levels in hairy cells. Additionally, we tested rapamycin treatment response of BONNA-12 wild-type cells or transfected with BRAFV600E. Most HCL cases expressed p-p70S6K and p-4E-BP1 but not p-mTOR, being accompanied by p-ERK1/2 and p-AKT. AKT/mTOR activation was evident in BONNA-12 cells irrespective of the presence of BRAFV600E mutation and was implicated in cell proliferation enhancement. In multivariate analysis p-AKT/p-mTOR/p-4E-BP1 overexpression was an adverse prognostic factor for time to next treatment conferring earlier relapse. When p-AKT, p-mTOR and p-4E-BP1 were examined separately only p-4E-BP1 remained significant. Our findings indicate that in HCL, critical proteins up- and downstream of mTOR are activated. Moreover, the strong associations with Raf-MEK-ERK signalling imply a possible biologic interaction between these pathways. Most importantly, expression of p-4E-BP1 alone or combined with p-AKT and p-mTOR is of prognostic value in patients with HCL.
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- art (subject category)
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- By the author/editor
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Lakiotaki, E
-
Levidou, G
-
Angelopoulou, MK
-
Adamopoulos, C
-
Pangalis, G
-
Rassidakis, G
-
show more...
-
Vassilakopoulos, ...
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Gainaru, G
-
Flevari, P
-
Sachanas, S
-
Saetta, AA
-
Sepsa, A
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Moschogiannis, M
-
Kalpadakis, C
-
Tsesmetzis, N
-
Milionis, V
-
Chatziandreou, I
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Thymara, I
-
Panayiotidis, P
-
Dimopoulou, M
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Plata, E
-
Konstantopoulos, ...
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Patsouris, E
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Piperi, C
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Korkolopoulou, P
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show less...
- Articles in the publication
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Scientific repor ...
- By the university
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Karolinska Institutet