The role of TGFβ in hematopoiesis and myeloid disorders

被引:51
作者
Bataller, Alex [1 ]
Montalban-Bravo, Guillermo [2 ]
Soltysiak, Kelly A. [2 ]
Garcia-Manero, Guillermo [2 ]
机构
[1] Hosp Clin Barcelona, Dept Hematol, IDIBAPS, Barcelona, Spain
[2] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
关键词
GROWTH-FACTOR-BETA; BONE-MARROW NICHE; MYELODYSPLASTIC SYNDROMES; LIGAND TRAP; ERYTHROID-DIFFERENTIATION; TRANSFORMING GROWTH-FACTOR-BETA-1; SIGNALING PATHWAY; DOUBLE-BLIND; STEM-CELLS; ACTIVIN-A;
D O I
10.1038/s41375-019-0420-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The role of transforming growth factor-beta (TGF beta) signaling in embryological development and tissue homeostasis has been thoroughly characterized. Its canonical downstream cascade is well known, even though its true complexity and other noncanonical pathways are still being explored. TGF beta signaling has been described as an important pathway involved in carcinogenesis and cancer progression. In the hematopoietic compartment, the TGF beta pathway is an important regulator of proliferation and differentiation of different cell types and has been implicated in the pathogenesis of a diverse variety of bone marrow disorders. Due to its importance in hematological diseases, novel inhibitors of this pathway are being developed against a number of hematopoietic disorders, including myelodysplastic syndromes (MDS). In this review, we provide an overview of the TGF beta pathway, focusing on its role in hematopoiesis and impact on myeloid disorders. We will discuss therapeutic interventions with promising results against MDS.
引用
收藏
页码:1076 / 1089
页数:14
相关论文
共 116 条
  • [1] Sotatercept in patients with osteolytic lesions of multiple myeloma
    Abdulkadyrov, Kudrat M.
    Salogub, Galina N.
    Khuazheva, Nuriet K.
    Sherman, Matthew L.
    Laadem, Abderrahmane
    Barger, Rachel
    Knight, Robert
    Srinivasan, Shankar
    Terpos, Evangelos
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2014, 165 (06) : 814 - 823
  • [2] Human T-cell lymphotropic virus oncoprotein Tax represses TGF-β1 signaling in human T cells via c-Jun activation:: a potential mechanism of HTLV-I leukemogenesis
    Arnulf, B
    Villemain, A
    Nicot, C
    Mordelet, E
    Charneau, P
    Kersual, J
    Zermati, Y
    Mauviel, A
    Bazarbachi, A
    Hermine, O
    [J]. BLOOD, 2002, 100 (12) : 4129 - 4138
  • [3] Bcr-Abl activates the AKT/FoxO3 signalling pathway to restrict transforming growth factor-β-mediated cytostatic signals
    Atfi, A
    Abécassis, L
    Bourgeade, MF
    [J]. EMBO REPORTS, 2005, 6 (10) : 985 - 991
  • [4] A phase 1 study of ACE-536, a regulator of erythroid differentiation, in healthy volunteers
    Attie, Kenneth M.
    Allison, Mark J.
    McClure, Ty
    Boyd, Ingrid E.
    Wilson, Dawn M.
    Pearsall, Amelia E.
    Sherman, Matthew L.
    [J]. AMERICAN JOURNAL OF HEMATOLOGY, 2014, 89 (07) : 766 - 770
  • [5] Smads as transcriptional co-modulators
    Attisano, L
    Wrana, JL
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (02) : 235 - 243
  • [6] Batard P, 2000, J CELL SCI, V113, P383
  • [7] miR-21 mediates hematopoietic suppression in MDS by activating TGF-β signaling
    Bhagat, Tushar D.
    Zhou, Li
    Sokol, Lubomir
    Kessel, Rachel
    Caceres, Gisela
    Gundabolu, Krishna
    Tamari, Roni
    Gordon, Shanisha
    Mantzaris, Ioannis
    Jodlowski, Tomasz
    Yu, Yiting
    Jing, Xiaohong
    Polineni, Rahul
    Bhatia, Kavi
    Pellagatti, Andrea
    Boultwood, Jacqueline
    Kambhampati, Suman
    Steidl, Ulrich
    Stein, Cy
    Ju, Wenjun
    Liu, Gang
    Kenny, Paraic
    List, Alan
    Bitzer, Markus
    Verma, Amit
    [J]. BLOOD, 2013, 121 (15) : 2875 - 2881
  • [8] TGF-β signaling in the control of hematopoietic stem cells
    Blank, Ulrika
    Karlsson, Stefan
    [J]. BLOOD, 2015, 125 (23) : 3542 - 3550
  • [9] A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: The skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells
    Borkowski, TA
    Letterio, JJ
    Farr, AG
    Udey, MC
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (06) : 2417 - 2422
  • [10] Myelodysplasia is in the niche: novel concepts and emerging therapies
    Bulycheva, E.
    Rauner, M.
    Medyouf, H.
    Theurl, I.
    Bornhaeuser, M.
    Hofbauer, L. C.
    Platzbecker, U.
    [J]. LEUKEMIA, 2015, 29 (02) : 259 - 268