A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

Sebastian Kollmann; Reinhard Grausenburger; Thorsten Klampfl; Michaela Prchal-Murphy; Klavdija Bastl; Hanja Pisa; Vanessa M. Knab; Tania Brandstoetter; Eszter Doma; Wolfgang R. Sperr; Sabine Lagger; Matthias Farlik; Richard Moriggl; Peter Valent; Florian Halbritter; Karoline Kollmann; Gerwin Heller; Barbara Maurer; Veronika Sexl

doi:10.1182/blood.2021010980

A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

Sebastian Kollmann
, Reinhard Grausenburger
, Thorsten Klampfl
, Michaela Prchal-Murphy
, Klavdija Bastl
, Hanja Pisa
, Vanessa M. Knab
, Tania Brandstoetter
, Eszter Doma
, Wolfgang R. Sperr
, Sabine Lagger
, Matthias Farlik
, Richard Moriggl
, Peter Valent
, Florian Halbritter
, Karoline Kollmann
, Gerwin Heller
, Barbara Maurer
, Veronika Sexl

Publikation: Wissenschaftliche Fachzeitschrift › Originalbeitrag in Fachzeitschrift › Begutachtung

Abstract

The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia, and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.

Originalsprache	Englisch
Seiten (von - bis)	2347–2359
Fachzeitschrift	Blood
Volume	138
Ausgabenummer	23
DOIs	https://doi.org/10.1182/blood.2021010980
Publikationsstatus	Veröffentlicht - 9 Dez. 2021
Extern publiziert	Ja

Zugriff auf Dokument

10.1182/blood.2021010980

Zitat

Kollmann, S., Grausenburger, R., Klampfl, T., Prchal-Murphy, M., Bastl, K., Pisa, H., Knab, V. M., Brandstoetter, T., Doma, E., Sperr, W. R., Lagger, S., Farlik, M., Moriggl, R., Valent, P., Halbritter, F., Kollmann, K., Heller, G., Maurer, B., & Sexl, V. (2021). A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells. Blood, 138(23), 2347–2359. https://doi.org/10.1182/blood.2021010980

@article{de8c19b4afed47c08df536e906699aa4,

title = "A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells",

abstract = "The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia, and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.",

author = "Sebastian Kollmann and Reinhard Grausenburger and Thorsten Klampfl and Michaela Prchal-Murphy and Klavdija Bastl and Hanja Pisa and Knab, \{Vanessa M.\} and Tania Brandstoetter and Eszter Doma and Sperr, \{Wolfgang R.\} and Sabine Lagger and Matthias Farlik and Richard Moriggl and Peter Valent and Florian Halbritter and Karoline Kollmann and Gerwin Heller and Barbara Maurer and Veronika Sexl",

year = "2021",

month = dec,

day = "9",

doi = "10.1182/blood.2021010980",

language = "English",

volume = "138",

pages = "2347–2359",

journal = "Blood",

issn = "0006-4971",

publisher = "Elsevier B.V.",

number = "23",

}

Kollmann, S, Grausenburger, R, Klampfl, T, Prchal-Murphy, M, Bastl, K, Pisa, H, Knab, VM, Brandstoetter, T, Doma, E, Sperr, WR, Lagger, S, Farlik, M, Moriggl, R, Valent, P, Halbritter, F, Kollmann, K, Heller, G, Maurer, B & Sexl, V 2021, 'A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells', Blood, Jg. 138, Nr. 23, S. 2347–2359. https://doi.org/10.1182/blood.2021010980

TY - JOUR

T1 - A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

AU - Kollmann, Sebastian

AU - Grausenburger, Reinhard

AU - Klampfl, Thorsten

AU - Prchal-Murphy, Michaela

AU - Bastl, Klavdija

AU - Pisa, Hanja

AU - Knab, Vanessa M.

AU - Brandstoetter, Tania

AU - Doma, Eszter

AU - Sperr, Wolfgang R.

AU - Lagger, Sabine

AU - Farlik, Matthias

AU - Moriggl, Richard

AU - Valent, Peter

AU - Halbritter, Florian

AU - Kollmann, Karoline

AU - Heller, Gerwin

AU - Maurer, Barbara

AU - Sexl, Veronika

PY - 2021/12/9

Y1 - 2021/12/9

N2 - The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia, and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.

AB - The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia, and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.

U2 - 10.1182/blood.2021010980

DO - 10.1182/blood.2021010980

M3 - Journal article

SN - 0006-4971

VL - 138

SP - 2347

EP - 2359

JO - Blood

JF - Blood

IS - 23

ER -