Literature DB >> 20008790

Stem cell exhaustion due to Runx1 deficiency is prevented by Evi5 activation in leukemogenesis.

Bindya Jacob1, Motomi Osato, Namiko Yamashita, Chelsia Qiuxia Wang, Ichiro Taniuchi, Dan R Littman, Norio Asou, Yoshiaki Ito.   

Abstract

The RUNX1/AML1 gene is the most frequently mutated gene in human leukemia. Conditional deletion of Runx1 in adult mice results in an increase of hematopoietic stem cells (HSCs), which serve as target cells for leukemia; however, Runx1(-/-) mice do not develop spontaneous leukemia. Here we show that maintenance of Runx1(-/-) HSCs is compromised, progressively resulting in HSC exhaustion. In leukemia development, the stem cell exhaustion was rescued by additional genetic changes. Retroviral insertional mutagenesis revealed Evi5 activation as a cooperating genetic alteration and EVI5 overexpression indeed prevented Runx1(-/-) HSC exhaustion in mice. Moreover, EVI5 was frequently overexpressed in human RUNX1-related leukemias. These results provide insights into the mechanism for maintenance of pre-leukemic stem cells and may provide a novel direction for therapeutic applications.

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Year:  2009        PMID： 20008790      PMCID： PMC2830765          DOI： 10.1182/blood-2009-07-232249

Source DB:  PubMed          Journal:  Blood        ISSN： 0006-4971            Impact factor:   22.113


  42 in total

1.  The fusion gene Cbfb-MYH11 blocks myeloid differentiation and predisposes mice to acute myelomonocytic leukaemia.

Authors:  L H Castilla; L Garrett; N Adya; D Orlic; A Dutra; S Anderson; J Owens; M Eckhaus; D Bodine; P P Liu
Journal:  Nat Genet       Date:  1999-10       Impact factor: 38.330

2.  Cooperating cancer-gene identification through oncogenic-retrovirus-induced insertional mutagenesis.

Authors:  Yang Du; Sally E Spence; Nancy A Jenkins; Neal G Copeland
Journal:  Blood       Date:  2005-06-16       Impact factor: 22.113

3.  Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia.

Authors:  W J Song; M G Sullivan; R D Legare; S Hutchings; X Tan; D Kufrin; J Ratajczak; I C Resende; C Haworth; R Hock; M Loh; C Felix; D C Roy; L Busque; D Kurnit; C Willman; A M Gewirtz; N A Speck; J H Bushweller; F P Li; K Gardiner; M Poncz; J M Maris; D G Gilliland
Journal:  Nat Genet       Date:  1999-10       Impact factor: 38.330

4.  Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia.

Authors:  B F Goemans; C M Zwaan; M Miller; M Zimmermann; A Harlow; S Meshinchi; A H Loonen; K Hählen; D Reinhardt; U Creutzig; G J L Kaspers; M C Heinrich
Journal:  Leukemia       Date:  2005-09       Impact factor: 11.528

5.  Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment.

Authors:  Lei Wang; Linda Yang; Marie-Dominique Filippi; David A Williams; Yi Zheng
Journal:  Blood       Date:  2005-09-20       Impact factor: 22.113

6.  Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression.

Authors:  Hiromi Yuasa; Yuichi Oike; Atsushi Iwama; Ichiro Nishikata; Daisuke Sugiyama; Archibald Perkins; Michael L Mucenski; Toshio Suda; Kazuhiro Morishita
Journal:  EMBO J       Date:  2005-05-12       Impact factor: 11.598

7.  Haploinsufficiency of Runx1/AML1 promotes myeloid features and leukaemogenesis in BXH2 mice.

Authors:  Namiko Yamashita; Motomi Osato; Liqun Huang; Masatoshi Yanagida; Scott C Kogan; Masayuki Iwasaki; Takuro Nakamura; Katsuya Shigesada; Norio Asou; Yoshiaki Ito
Journal:  Br J Haematol       Date:  2005-11       Impact factor: 6.998

8.  Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype.

Authors:  Joseph D Growney; Hirokazu Shigematsu; Zhe Li; Benjamin H Lee; Jennifer Adelsperger; Rebecca Rowan; David P Curley; Jeffery L Kutok; Koichi Akashi; Ifor R Williams; Nancy A Speck; D Gary Gilliland
Journal:  Blood       Date:  2005-03-22       Impact factor: 22.113

9.  Increased dosage of Runx1/AML1 acts as a positive modulator of myeloid leukemogenesis in BXH2 mice.

Authors:  Masatoshi Yanagida; Motomi Osato; Namiko Yamashita; Huang Liqun; Bindya Jacob; Feng Wu; Xinmin Cao; Takuro Nakamura; Tomomasa Yokomizo; Satoru Takahashi; Masayuki Yamamoto; Katsuya Shigesada; Yoshiaki Ito
Journal:  Oncogene       Date:  2005-06-30       Impact factor: 9.867

Review 10.  Retroviral insertional mutagenesis identifies oncogene cooperation.

Authors:  Takuro Nakamura
Journal:  Cancer Sci       Date:  2005-01       Impact factor: 6.716
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  50 in total

1.  A Src family kinase-Shp2 axis controls RUNX1 activity in megakaryocyte and T-lymphocyte differentiation.

Authors:  Hui Huang; Andrew J Woo; Zachary Waldon; Yocheved Schindler; Tyler B Moran; Helen H Zhu; Gen-Sheng Feng; Hanno Steen; Alan B Cantor
Journal:  Genes Dev       Date:  2012-07-03       Impact factor: 11.361

2.  FLIP: a novel regulator of macrophage differentiation and granulocyte homeostasis.

Authors:  Qi-Quan Huang; Harris Perlman; Zan Huang; Robert Birkett; Lixin Kan; Hemant Agrawal; Alexander Misharin; Sandeep Gurbuxani; John D Crispino; Richard M Pope
Journal:  Blood       Date:  2010-08-19       Impact factor: 22.113

Review 3.  The RUNX complex: reaching beyond haematopoiesis into immunity.

Authors:  Dominic Chih-Cheng Voon; Yit Teng Hor; Yoshiaki Ito
Journal:  Immunology       Date:  2015-10-25       Impact factor: 7.397

Review 4.  Posttranslational modifications of RUNX1 as potential anticancer targets.

Authors:  S Goyama; G Huang; M Kurokawa; J C Mulloy
Journal:  Oncogene       Date:  2014-09-29       Impact factor: 9.867

5.  Cbfb deficiency results in differentiation blocks and stem/progenitor cell expansion in hematopoiesis.

Authors:  C Q Wang; D W L Chin; J Y Chooi; W J Chng; I Taniuchi; V Tergaonkar; M Osato
Journal:  Leukemia       Date:  2014-11-05       Impact factor: 11.528

6.  A Runx1-Smad6 rheostat controls Runx1 activity during embryonic hematopoiesis.

Authors:  Kathy Knezevic; Thomas Bee; Nicola K Wilson; Mary E Janes; Sarah Kinston; Stéphanie Polderdijk; Anja Kolb-Kokocinski; Katrin Ottersbach; Niv Pencovich; Yoram Groner; Marella de Bruijn; Berthold Göttgens; John E Pimanda
Journal:  Mol Cell Biol       Date:  2011-05-16       Impact factor: 4.272

7.  The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells.

Authors:  Philipp B Staber; Pu Zhang; Min Ye; Robert S Welner; Elena Levantini; Annalisa Di Ruscio; Alexander K Ebralidze; Christian Bach; Hong Zhang; Junyan Zhang; Katrina Vanura; Ruud Delwel; Henry Yang; Gang Huang; Daniel G Tenen
Journal:  Blood       Date:  2014-09-03       Impact factor: 22.113

Review 8.  A role for RUNX1 in hematopoiesis and myeloid leukemia.

Authors:  Motoshi Ichikawa; Akihide Yoshimi; Masahiro Nakagawa; Nahoko Nishimoto; Naoko Watanabe-Okochi; Mineo Kurokawa
Journal:  Int J Hematol       Date:  2013-04-24       Impact factor: 2.490

9.  Internal tandem duplication of FLT3 deregulates proliferation and differentiation and confers resistance to the FLT3 inhibitor AC220 by Up-regulating RUNX1 expression in hematopoietic cells.

Authors:  Tomohiro Hirade; Mariko Abe; Chie Onishi; Takeshi Taketani; Seiji Yamaguchi; Seiji Fukuda
Journal:  Int J Hematol       Date:  2015-11-21       Impact factor: 2.490

10.  Expression of the runt homology domain of RUNX1 disrupts homeostasis of hematopoietic stem cells and induces progression to myelodysplastic syndrome.

Authors:  Shinobu Matsuura; Yukiko Komeno; Kristen E Stevenson; Joseph R Biggs; Kentson Lam; Tingdong Tang; Miao-Chia Lo; Xiuli Cong; Ming Yan; Donna S Neuberg; Dong-Er Zhang
Journal:  Blood       Date:  2012-08-23       Impact factor: 22.113
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