LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10323622" target="_blank" >RIV/00064203:_____/16:10323622 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/16:10323622

Result on the web

<a href="http://dx.doi.org/10.1182/blood-2015-09-667808" target="_blank" >http://dx.doi.org/10.1182/blood-2015-09-667808</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1182/blood-2015-09-667808" target="_blank" >10.1182/blood-2015-09-667808</a>

Result language

angličtina

Original language name

LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia

Original language description

Juvenile myelomonocytic leukemia (JMML) is a rare and aggressive stem cell disease of early childhood. RAS activation constitutes the core component of oncogenic signaling. In addition, leukemic blasts in one-fourth of JMML patients present with monosomy 7, and more than half of patients show elevated age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care and results in an event-free survival rate of 50% to 60%, indicating that novel molecular-driven therapeutic options are urgently needed. Using gene expression profiling in a series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression. LIN28B overexpression was significantly correlated with higher HbF levels, whereas patients with monosomy 7 seldom showed enhanced LIN28B expression. This finding gives a biological explanation of why patients with monosomy 7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7 microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Lastly, high LIN28B expression was associated with poor clinical outcome in our JMML patient series but was not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified elevated LIN28B expression as a hallmark of a novel fetal-like subgroup in JMML.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

—

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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

Name of the periodical

Blood

ISSN

0006-4971

e-ISSN

—

Volume of the periodical

127

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

1163-1172

UT code for WoS article

000373401700016

EID of the result in the Scopus database

2-s2.0-84960411158