High activation of STAT5A drives peripheral T-cell lymphoma and leukemia
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00116030" target="_blank" >RIV/00216224:14740/20:00116030 - isvavai.cz</a>
Alternative codes found
RIV/65269705:_____/20:00072658
Result on the web
<a href="http://www.haematologica.org/content/haematol/105/2/435.full.pdf" target="_blank" >http://www.haematologica.org/content/haematol/105/2/435.full.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3324/haematol.2019.216986" target="_blank" >10.3324/haematol.2019.216986</a>
Alternative languages
Result language
angličtina
Original language name
High activation of STAT5A drives peripheral T-cell lymphoma and leukemia
Original language description
Recurrent gain-of-function mutations in the transcription factors S7AT5A and much more in STAT5B were found in hematopoietic malignancies with the highest proportion in mature T- and natural killer-cell neoplasms (peripheral T-cell lymphoma, PTCL). No targeted therapy exists for these heterogeneous and often aggressive diseases. Given the shortage of models for PTCL, we mimicked graded STAT5A or STAT5B activity by expressing hyperactive Stat5a or STAT5B variants at low or high levels in the hematopoietic system of transgenic mice. Only mice with high activity levels developed a lethal disease resembling human PTCL. Neoplasia displayed massive expansion of CD8(+) T cells and destructive organ infiltration. T cells were cytokine-hypersensitive with activated memory CD8(+). T-lymphocyte characteristics. Histopathology and mRNA expression profiles revealed close correlation with distinct subtypes of PTCL. Pronounced STAT5 expression and activity in samples from patients with different subsets underline the relevance of JAK/STAT as a therapeutic target. JAK inhibitors or a selective STAT5 SH2 domain inhibitor induced cell death and ruxolitinib blocked T-cell neoplasia in vivo. We conclude that enhanced STAT5A or STAT5B action both drive PTCL development, defining both STAT5 molecules as targets for therapeutic intervention.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30205 - Hematology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Haematologica
ISSN
0390-6078
e-ISSN
—
Volume of the periodical
105
Issue of the periodical within the volume
2
Country of publishing house
IT - ITALY
Number of pages
13
Pages from-to
435-447
UT code for WoS article
000510846700034
EID of the result in the Scopus database
2-s2.0-85078816456