New concepts in follicular lymphoma biology: From BCL2 to epigenetic regulators and non-coding RNAs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F18%3A00105658" target="_blank" >RIV/00216224:14740/18:00105658 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/65269705:_____/18:00069102

Výsledek na webu

<a href="http://dx.doi.org/10.1053/j.seminoncol.2018.07.005" target="_blank" >http://dx.doi.org/10.1053/j.seminoncol.2018.07.005</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1053/j.seminoncol.2018.07.005" target="_blank" >10.1053/j.seminoncol.2018.07.005</a>

Jazyk výsledku

angličtina

Název v původním jazyce

New concepts in follicular lymphoma biology: From BCL2 to epigenetic regulators and non-coding RNAs

Popis výsledku v původním jazyce

The molecular pathogenesis of follicular lymphoma (FL) was partially revealed 3 decades ago, with the discovery of the translocation that brings BCL2 under the influence of immunoglobulin heavy chain enhancers in a vast majority of cases. Despite the importance of this seminal observation, it has become increasingly clear that additional genetic alterations need to occur to trigger neoplastic transformation and disease progression. The evolution of FL involves developmental arrest and disruption of the normal function of one or more of epigenetic regulators including KMT2D/MLL2, EZH2, CBP/CREBBP, p300/EP300, and HIST1H1 in &gt;95% of cases. B-cells "arrested" in germinal centers acquire dozens of additional genetic aberrations that influence key pathways controlling their physiological development including B Cell Receptor (BCR) signaling, PI3K/AKT, TLR, mTOR, NF-kappa B, JAK/STAT, MAPK, CD40/CD4OL, chemokine, and interleukin signaling. Additionally, most cases of FL do not result from linear accumulation of genomic aberrations, but rather evolve from a common progenitor cell population by diverse evolution, creating multiple FL subclones in one patient. Moreover, one of the subclones might acquire a combination of aberrations involving genes controlling cell survival and proliferation including MDM2, CDKN2A/B, BCL6, MYC, TP53, beta 2M, FOXO1, MYD88, STAT3, or miR-17-92, and this can lead to the transformation of an initially indolent FL to an aggressive lymphoma (2%-3% risk per year). The complexity of the disease is also underscored by the importance of its interactions with the microenvironment that can substantially influence disease development and prognosis. Interpreting individual aberrations in relation to their impact on normal processes, their frequency, position in the disease evolution, and the consequences of their (co)occurrence, are the basis for understanding FL pathogenesis. This is necessary for the identification of patients with risk of early progression or transformation, for the development of novel targeted therapies, and for personalized treatment approaches. In this review, we summarize recent knowledge of molecular pathways and microenvironmental components involved in FL biology, and discuss them in the context of physiological B-cell development, FL evolution, and targeted therapies. (C) 2018 Elsevier Inc. All rights reserved.

Název v anglickém jazyce

New concepts in follicular lymphoma biology: From BCL2 to epigenetic regulators and non-coding RNAs

Popis výsledku anglicky

The molecular pathogenesis of follicular lymphoma (FL) was partially revealed 3 decades ago, with the discovery of the translocation that brings BCL2 under the influence of immunoglobulin heavy chain enhancers in a vast majority of cases. Despite the importance of this seminal observation, it has become increasingly clear that additional genetic alterations need to occur to trigger neoplastic transformation and disease progression. The evolution of FL involves developmental arrest and disruption of the normal function of one or more of epigenetic regulators including KMT2D/MLL2, EZH2, CBP/CREBBP, p300/EP300, and HIST1H1 in &gt;95% of cases. B-cells "arrested" in germinal centers acquire dozens of additional genetic aberrations that influence key pathways controlling their physiological development including B Cell Receptor (BCR) signaling, PI3K/AKT, TLR, mTOR, NF-kappa B, JAK/STAT, MAPK, CD40/CD4OL, chemokine, and interleukin signaling. Additionally, most cases of FL do not result from linear accumulation of genomic aberrations, but rather evolve from a common progenitor cell population by diverse evolution, creating multiple FL subclones in one patient. Moreover, one of the subclones might acquire a combination of aberrations involving genes controlling cell survival and proliferation including MDM2, CDKN2A/B, BCL6, MYC, TP53, beta 2M, FOXO1, MYD88, STAT3, or miR-17-92, and this can lead to the transformation of an initially indolent FL to an aggressive lymphoma (2%-3% risk per year). The complexity of the disease is also underscored by the importance of its interactions with the microenvironment that can substantially influence disease development and prognosis. Interpreting individual aberrations in relation to their impact on normal processes, their frequency, position in the disease evolution, and the consequences of their (co)occurrence, are the basis for understanding FL pathogenesis. This is necessary for the identification of patients with risk of early progression or transformation, for the development of novel targeted therapies, and for personalized treatment approaches. In this review, we summarize recent knowledge of molecular pathways and microenvironmental components involved in FL biology, and discuss them in the context of physiological B-cell development, FL evolution, and targeted therapies. (C) 2018 Elsevier Inc. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/NV18-03-00054" target="_blank" >NV18-03-00054: ÚLOHA MICRORNA A JEJICH CÍLOVÝCH MOLEKUL V TRANSFORMACI FOLIKULÁRNÍHO LYMFOMU A AGRESIVITĚ CHRONICKÉ LYMFOCYTÁRNÍ LEUKÉMIE</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

SEMINARS IN ONCOLOGY

ISSN

0093-7754

e-ISSN

—

Svazek periodika

45

Číslo periodika v rámci svazku

5-6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

291-302

Kód UT WoS článku

000454187700005

EID výsledku v databázi Scopus

2-s2.0-85055130153