Vol 4, No 2 (2013)
Review paper
Published online: 2013-06-25
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PI3K-AKT axis in normal lymphoid development and B-cell tumors. Part I
Hematologia 2013;4(2):103-113.
Abstract
Understanding the role of signalling pathways in the pathogenesis of B-cell malignancies requires
elucidation of their function in the normal B cell ontogeny. Studies performed so far underscore
the role of the PI3K-AKT signalling cascade and its downstream effectors, especially FOXO
transcription factors, in control of B cell development and in the pathogenesis of various B-cell
tumors. PI3K-AKT-FOXO axis is known to regulate key processes in B cells, such as proliferation,
cell cycle, apoptosis, oxidative stress or DNA damage repair. Herein, we review molecular mechanisms
of the PI3K-AKT-dependent signal transduction, mechanisms modulating activity of the axis
and their impact on early B cell development, peripherial B cell homeostasis and terminal B-cell
differentiation. In the next part of the review, functional consequences of the PI3K-Akt -Foxo
signalling deregulation in B-cell tumors and potential use of molecules modulating activity of the
axis in the treatment of B-cell malignancies will be discussed.
elucidation of their function in the normal B cell ontogeny. Studies performed so far underscore
the role of the PI3K-AKT signalling cascade and its downstream effectors, especially FOXO
transcription factors, in control of B cell development and in the pathogenesis of various B-cell
tumors. PI3K-AKT-FOXO axis is known to regulate key processes in B cells, such as proliferation,
cell cycle, apoptosis, oxidative stress or DNA damage repair. Herein, we review molecular mechanisms
of the PI3K-AKT-dependent signal transduction, mechanisms modulating activity of the axis
and their impact on early B cell development, peripherial B cell homeostasis and terminal B-cell
differentiation. In the next part of the review, functional consequences of the PI3K-Akt -Foxo
signalling deregulation in B-cell tumors and potential use of molecules modulating activity of the
axis in the treatment of B-cell malignancies will be discussed.
Keywords: B cell developmentPI3K-AKTFOXO
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