Top

Published in:

01-09-2015 | Original Article

HES1 activation suppresses proliferation of leukemia cells in acute myeloid leukemia

Authors: Chen Tian, Yong Yu, Yongsheng Jia, Lei Zhu, Yizhuo Zhang

Published in: Annals of Hematology | Issue 9/2015

Abstract

Although aberrant Notch activation contributes to leukemogenesis in T cells, the role of Notch pathway in acute myeloid leukemia (AML) remains controversial. To address this issue, we compared the expression levels of its downstream effector HES1 and p21 in bone marrow mononuclear cells (BMNCs) from 30 newly diagnosed AML patients and three AML cell lines to normal BMNCs. The results showed that both of them were downregulated in AML cells. In vitro, induced activation of HES1 by retrovirus in AML cell lines consistently led to AML cell growth arrest and apoptosis induction, which was associated with enhanced p21 expression. Furthermore, overexpression of HES1 in primary AML cells inhibited growth of AML in a xenograft mice model. In conclusion, we demonstrated the tumor suppressor role of HES1 in AML.

Aster JC, Pear WS, Blacklow SC (2008) Notch signaling in leukemia. Annu Rev Pathol 3:587–613PubMedCrossRef

Xu X, Zhao Y, Xu M, Dai Q, Meng W, Yang J et al (2011) Activation of Notch signal pathway is associated with a poorer prognosis in acute myeloid leukemia. Med Oncol 28:S483–S489PubMedCrossRef

Chadwick N, Nostro MC, Baron M, Mottram R, Brady G, Buckle AM (2007) Notch signaling induces apoptosis in primary human CD34+ hematopoietic progenitor cells. Stem Cells 25:203–210PubMedCrossRef

Lobry C, Oh P, Aifantis I (2011) Oncogenic and tumor suppressor functions of Notch in cancer: it’s NOTCH what you think. J Exp Med 208(10):1931–1935PubMedCentralPubMedCrossRef

Li GH, Fan YZ, Liu XW, Zhang BF, Yin DD, He F et al (2010) Notch signaling maintains proliferation and survival of the HL60 human promyelocytic leukemia cell line and promotes the phosphorylation of the Rb protein. Mol Cell Biochem 340(1–2):7–14PubMedCrossRef

Lobry C, Ntziachristos P, Ndiaye-Lobry D, Oh P, Cimmino L, Zhu N et al (2013) Notch pathway activation targets AML initiating cell homeostasis and differentiation. J Exp Med 210(2):301–319PubMedCentralPubMedCrossRef

Kannan S, Sutphin RM, Hall MG, Golfman LS, Fang W, Nolo RM et al (2013) Notch activation inhibits AML growth and survival: a potential therapeutic approach. J Exp Med 210(2):321–337PubMedCentralPubMedCrossRef

Nakahara F, Sakata-Yanagimoto M, Komeno Y, Kato N, Uchida T, Haraguchi K et al (2010) HES1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia. Blood 115(14):2872–2881PubMedCrossRef

Tian C, Zheng G, Cao Z, Li Q, Ju Z, Wang J et al (2013) HES1 mediates the different responses of hematopoietic stem and progenitor cells to T cell leukemic environment. Cell Cycle 12(2):322–331PubMedCentralPubMedCrossRef

10.

Kato T, Sakata-Yanagimoto M, Nishikii H, Ueno M, Miyake Y, Yokoyama Y et al (2015) HES1 suppresses acute myeloid leukemia development through FLT3 repression. Leukemia 29(3):576–585PubMedCrossRef

11.

Hughes DP (2010) How the Notch pathway contributes to the ability of osteosarcoma cells to metastasize. Cancer Treat Res 152:479–496CrossRef

12.

Kanamori E, Itoh M, Tojo N, Koyama T, Nara N, Tohda S (2012) Flow cytometric analysis of Notch1 and Jagged1 expression in normal blood cells and leukemia cells. Exp Ther Med 4(3):397–400PubMedCentralPubMed

13.

Mirandola L, Apicella L, Colombo M, Yu Y, Berta DG, Platonova N et al (2013) Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4/SDF-1. Leukemia 27(7):1558–1566PubMedCrossRef

14.

Tohda S, Nara N (2001) Expression of Notch1 and Jagged1 proteins in acute myeloid leukemia cells. Leuk Lymphoma 42:467–472PubMedCrossRef

15.

Tohda S, Kogoshi H, Murakami N, Sakano S, Nara N (2005) Diverse effects of the Notch ligands Jagged1 and Delta1 on the growth and differentiation of primary acute myeloblastic leukemia cells. Exp Hematol 33(5):558–563PubMedCrossRef

16.

Yin G, Hou R, Li J, Zhang J, Li X, Zhang K (2012) Expression of Notch receptor and its target gene HES1 in bone marrow CD34+ cells from patients with psoriasis. Dermatology 225(2):147–153PubMedCrossRef

17.

Vo TT, Ryan J, Carrasco R, Neuberg D, Rossi DJ, Stone RM et al (2012) Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML. Cell 151:344–355PubMedCentralPubMedCrossRef

18.

Del Giudice I, Rossi D, Chiaretti S, Marinelli M, Tavolaro S, Gabrielli S et al (2011) NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL. Haematologica 97:437–441PubMedCrossRef

19.

Klinakis A, Lobry C, Abdel-Wahab O, Oh P, Haeno H, Buonamici S et al (2011) A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia. Nature 473:230–233PubMedCentralPubMedCrossRef

20.

Yu X, Alder JK, Chun JH, Friedman AD, Heimfeld S, Cheng L et al (2006) HES1 inhibits cycling of hematopoietic progenitor cells via DNA binding. Stem Cells 24(4):876–888PubMedCrossRef

21.

Nwabo Kamdje AH, Mosna F, Bifari F, Lisi V, Bassi G, Malpeli G et al (2011) Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells. Blood 118(2):380–389PubMedCrossRef

22.

Dahlberg A, Delaney C, Bernstein ID (2011) Ex vivo expansion of human hematopoietic stem and progenitor cells. Blood 117:6083–6090PubMedCentralPubMedCrossRef

Title: HES1 activation suppresses proliferation of leukemia cells in acute myeloid leukemia
Authors: Chen Tian
Yong Yu
Yongsheng Jia
Lei Zhu
Yizhuo Zhang
Publication date: 01-09-2015
Publisher: Springer Berlin Heidelberg
Published in: Annals of Hematology / Issue 9/2015
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-015-2413-0

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2015

Effect of combined deferasirox and 5-azacytidine treatment on human leukemia cells in vitro

Headache prevalence following recovery from TTP and aHUS

Antiviral prophylaxis in patients with solid tumours and haematological malignancies—update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO)

Hospital population screening reveals overrepresentation of CD5− monoclonal B-cell lymphocytosis and monoclonal gammopathy of undetermined significance of IgM type

Negative PET: no guarantee of good prognosis in Hodgkin’s lymphoma

Trained clinical nurse specialists proficiently obtain bone marrow aspirates and trephine biopsies in a nearly painless procedure—a prospective evaluation study

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials