High activation of STAT5A drives peripheral T-cell lymphoma and
leukemia

J 2020

High activation of STAT5A drives peripheral T-cell lymphoma and leukemia

MAURER, B., H. NIVARTHI, B. WINGELHOFER, H. T. T. PHAM, M. SCHLEDERER et. al.

Základní údaje

Originální název

High activation of STAT5A drives peripheral T-cell lymphoma and leukemia

Autoři

MAURER, B. (40 Rakousko), H. NIVARTHI (40 Rakousko), B. WINGELHOFER (40 Rakousko), H. T. T. PHAM (40 Rakousko), M. SCHLEDERER (40 Rakousko), T. SUSKE (40 Rakousko), R. GRAUSENBURGER (40 Rakousko), A. I. SCHIEFER (40 Rakousko), M. PRCHAL-MURPHY (40 Rakousko), D. CHEN (40 Rakousko), S. WINKLER (40 Rakousko), O. MERKEL (40 Rakousko), C. KORNAUTH, M. HOFBAUER (40 Rakousko), B. HOCHGATTERER (40 Rakousko), G. HOERMANN (40 Rakousko), A. HOELBL-KOVACIC (40 Rakousko), J. PROCHAZKOVA (40 Rakousko), Cosimo LOBELLO (380 Itálie, domácí), A. A. CUMARASWAMY (124 Kanada), J. LATZKA (124 Kanada), M. KITZWOGERER (40 Rakousko), A. CHOTT (40 Rakousko), Andrea JANÍKOVÁ (203 Česká republika, domácí), Šárka POSPÍŠILOVÁ (203 Česká republika, garant, domácí), J. I. LOIZOU (40 Rakousko), S. KUBICEK (40 Rakousko), P. VALENT (40 Rakousko), T. KOLBE (40 Rakousko), F. GREBIEN (40 Rakousko), L. KENNER (40 Rakousko), P. T. GUNNING (826 Velká Británie a Severní Irsko), R. KRALOVICS (40 Rakousko), M. HERLING (276 Německo), M. MULLER (40 Rakousko), T. RULICKE (40 Rakousko), V. SEXL (40 Rakousko) a R. MORIGGL (40 Rakousko)

Vydání

Haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2020, 0390-6078

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Itálie

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.941

Kód RIV

RIV/00216224:14740/20:00116030

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.3324/haematol.2019.216986

UT WoS

000510846700034

Klíčová slova anglicky

EXPRESSION; MUTATIONS; SIGNATURES; LANDSCAPE; DIAGNOSIS; GENETICS; SYSTEMS; MODELS; SIGNAL; ALPHA

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 3. 3. 2021 14:21, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

675712, interní kód MU

Název: ALK Activation as a target of TRAanslational Science (ALKATRAS): Break free from cancer (Akronym: ALKATRAS)

Investor: Evropská unie, ALK Activation as a target of TRAanslational Science (ALKATRAS): Break free from cancer, MSCA Marie Skłodowska-Curie Actions (Excellent Science)

Citovat

MAURER, B., H. NIVARTHI, B. WINGELHOFER, H. T. T. PHAM, M. SCHLEDERER, T. SUSKE, R. GRAUSENBURGER, A. I. SCHIEFER, M. PRCHAL-MURPHY, D. CHEN, S. WINKLER, O. MERKEL, C. KORNAUTH, M. HOFBAUER, B. HOCHGATTERER, G. HOERMANN, A. HOELBL-KOVACIC, J. PROCHAZKOVA, Cosimo LOBELLO, A. A. CUMARASWAMY, J. LATZKA, M. KITZWOGERER, A. CHOTT, Andrea JANÍKOVÁ, Šárka POSPÍŠILOVÁ, J. I. LOIZOU, S. KUBICEK, P. VALENT, T. KOLBE, F. GREBIEN, L. KENNER, P. T. GUNNING, R. KRALOVICS, M. HERLING, M. MULLER, T. RULICKE, V. SEXL a R. MORIGGL. High activation of STAT5A drives peripheral T-cell lymphoma and leukemia. Haematologica. PAVIA: FERRATA STORTI FOUNDATION, 2020, roč. 105, č. 2, s. 435-447. ISSN 0390-6078. Dostupné z: https://dx.doi.org/10.3324/haematol.2019.216986.

@article{1670624,
   author = {Maurer, B. and Nivarthi, H. and Wingelhofer, B. and Pham, H. T. T. and Schlederer, M. and Suske, T. and Grausenburger, R. and Schiefer, A. I. and PrchalandMurphy, M. and Chen, D. and Winkler, S. and Merkel, O. and Kornauth, C. and Hofbauer, M. and Hochgatterer, B. and Hoermann, G. and HoelblandKovacic, A. and Prochazkova, J. and Lobello, Cosimo and Cumaraswamy, A. A. and Latzka, J. and Kitzwogerer, M. and Chott, A. and Janíková, Andrea and Pospíšilová, Šárka and Loizou, J. I. and Kubicek, S. and Valent, P. and Kolbe, T. and Grebien, F. and Kenner, L. and Gunning, P. T. and Kralovics, R. and Herling, M. and Muller, M. and Rulicke, T. and Sexl, V. and Moriggl, R.},
   article_location = {PAVIA},
   article_number = {2},
   doi = {http://dx.doi.org/10.3324/haematol.2019.216986},
   keywords = {EXPRESSION; MUTATIONS; SIGNATURES; LANDSCAPE; DIAGNOSIS; GENETICS; SYSTEMS; MODELS; SIGNAL; ALPHA},
   language = {eng},
   issn = {0390-6078},
   journal = {Haematologica},
   title = {High activation of STAT5A drives peripheral T-cell lymphoma and leukemia},
   url = {http://www.haematologica.org/content/haematol/105/2/435.full.pdf},
   volume = {105},
   year = {2020}
}

TY  - JOUR
ID  - 1670624
AU  - Maurer, B. - Nivarthi, H. - Wingelhofer, B. - Pham, H. T. T. - Schlederer, M. - Suske, T. - Grausenburger, R. - Schiefer, A. I. - Prchal-Murphy, M. - Chen, D. - Winkler, S. - Merkel, O. - Kornauth, C. - Hofbauer, M. - Hochgatterer, B. - Hoermann, G. - Hoelbl-Kovacic, A. - Prochazkova, J. - Lobello, Cosimo - Cumaraswamy, A. A. - Latzka, J. - Kitzwogerer, M. - Chott, A. - Janíková, Andrea - Pospíšilová, Šárka - Loizou, J. I. - Kubicek, S. - Valent, P. - Kolbe, T. - Grebien, F. - Kenner, L. - Gunning, P. T. - Kralovics, R. - Herling, M. - Muller, M. - Rulicke, T. - Sexl, V. - Moriggl, R.
PY  - 2020
TI  - High activation of STAT5A drives peripheral T-cell lymphoma and leukemia
JF  - Haematologica
VL  - 105
IS  - 2
SP  - 435-447
EP  - 435-447
PB  - FERRATA STORTI FOUNDATION
SN  - 03906078
KW  - EXPRESSION
KW  - MUTATIONS
KW  - SIGNATURES
KW  - LANDSCAPE
KW  - DIAGNOSIS
KW  - GENETICS
KW  - SYSTEMS
KW  - MODELS
KW  - SIGNAL
KW  - ALPHA
UR  - http://www.haematologica.org/content/haematol/105/2/435.full.pdf
L2  - http://www.haematologica.org/content/haematol/105/2/435.full.pdf
N2  - 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.
ER  -

MAURER, B., H. NIVARTHI, B. WINGELHOFER, H. T. T. PHAM, M. SCHLEDERER, T. SUSKE, R. GRAUSENBURGER, A. I. SCHIEFER, M. PRCHAL-MURPHY, D. CHEN, S. WINKLER, O. MERKEL, C. KORNAUTH, M. HOFBAUER, B. HOCHGATTERER, G. HOERMANN, A. HOELBL-KOVACIC, J. PROCHAZKOVA, Cosimo LOBELLO, A. A. CUMARASWAMY, J. LATZKA, M. KITZWOGERER, A. CHOTT, Andrea JANÍKOVÁ, Šárka POSPÍŠILOVÁ, J. I. LOIZOU, S. KUBICEK, P. VALENT, T. KOLBE, F. GREBIEN, L. KENNER, P. T. GUNNING, R. KRALOVICS, M. HERLING, M. MULLER, T. RULICKE, V. SEXL a R. MORIGGL. High activation of STAT5A drives peripheral T-cell lymphoma and leukemia. \textit{Haematologica}. PAVIA: FERRATA STORTI FOUNDATION, 2020, roč.~105, č.~2, s.~435-447. ISSN~0390-6078. Dostupné z: https://dx.doi.org/10.3324/haematol.2019.216986.

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