title: Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.
abstract: Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.
authors: Department of Medicine and Biosystemic Sciences, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.|Japan Society for the Promotion of Science, Tokyo, Japan.
authors: Yoshikane
authors: Y
authors: Kikushige
authors: Department of Medicine and Biosystemic Sciences, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan. toshmiya@intmed1.med.kyushu-u.ac.jp.
authors: Toshihiro
authors: T
authors: Miyamoto
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology
keywords: Chronic lymphocytic leukemia; Hematopoietic stem cell; Pre-leukemia/pre-lymphoma
references: Blood. 2012 Sep 27;120(13):2553-61
references: 22869790
references: J Clin Oncol. 2008 Sep 20;26(27):4497-503
references: 18662968
references: Nat Rev Cancer. 2010 Jan;10(1):37-50
references: 19956173
references: Nature. 2011 Mar 10;471(7337):189-95
references: 21390126
references: Sci Transl Med. 2014 May 28;6(238):238ra71
references: 24871132
references: Blood. 2003 Oct 15;102(8):2994-3002
references: 12829608
references: Nature. 2011 Jun 05;475(7354):101-5
references: 21642962
references: Cell. 2008 Feb 22;132(4):681-96
references: 18295583
references: Leukemia. 2010 Jan;24(1):133-40
references: 19946263
references: Blood. 2009 Jul 2;114(1):26-32
references: 19029437
references: Science. 2008 Mar 21;319(5870):1676-9
references: 18323416
references: Blood. 2004 Jun 15;103(12):4389-95
references: 14962897
references: Exp Hematol. 2014 Nov;42(11):955-65.e1-5
references: 25101977
references: Blood. 2004 Nov 1;104(9):2879-85
references: 15217826
references: Nature. 2009 Aug 13;460(7257):904-8
references: 19620960
references: Dev Cell. 2002 Jul;3(1):137-47
references: 12110174
references: Nature. 2009 Jun 4;459(7247):712-6
references: 19412163
references: Blood. 2009 Jul 2;114(1):33-7
references: 19420353
references: Blood. 2003 Jan 15;101(2):383-9
references: 12393558
references: N Engl J Med. 2005 Feb 24;352(8):804-15
references: 15728813
references: Cell. 2011 Oct 28;147(3):554-64
references: 22036564
references: J Exp Med. 1989 Jan 1;169(1):255-68
references: 2462608
references: N Engl J Med. 2011 Dec 29;365(26):2497-506
references: 22150006
references: Blood. 2004 Oct 15;104(8):2499-504
references: 15217828
references: Cancer Discov. 2014 Sep;4(9):1088-101
references: 24920063
references: Cancer Cell. 2011 Jul 12;20(1):25-38
references: 21723201
references: Blood. 1996 Jun 1;87(11):4789-96
references: 8639850
references: N Engl J Med. 2012 Mar 22;366(12):1090-8
references: 22417201
references: Nat Commun. 2013;4:1338
references: 23299888
references: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7521-6
references: 10861016
references: Cell. 2013 Feb 14;152(4):714-26
references: 23415222
references: Cell. 2012 Jul 20;150(2):264-78
references: 22817890
references: J Autoimmun. 1988 Oct;1(5):469-81
references: 2473761
references: Nat Genet. 2014 Feb;46(2):171-5
references: 24413737
references: Nature. 2011 Sep 11;478(7367):64-9
references: 21909114
references: N Engl J Med. 2009 Feb 12;360(7):659-67
references: 19213679
references: Nat Genet. 2011 Dec 11;44(1):47-52
references: 22158541
references: Blood. 2012 Aug 16;120(7):1466-9
references: 22760778
references: Cancer Cell. 2011 Aug 16;20(2):246-59
references: 21840488
references: Nat Genet. 2010 Feb;42(2):181-5
references: 20081860
references: J Exp Med. 2012 Nov 19;209(12):2183-98
references: 23091163
references: Nature. 2012 Jan 11;481(7382):506-10
references: 22237025
references: J Exp Med. 2004 Aug 16;200(4):519-25
references: 15314077
references: Blood. 2014 Feb 27;123(9):1319-26
references: 24345750
references: Blood. 2012 Feb 23;119(8):1901-3
references: 22215888
references: Nat Genet. 2014 Feb;46(2):176-181
references: 24362818
references: Sci Transl Med. 2012 Aug 29;4(149):149ra118
references: 22932223
references: Br J Haematol. 2005 Aug;130(3):325-32
references: 16042682
references: Int J Hematol. 2014 Oct;100(4):335-40
references: 25100497
references: Blood. 1990 Aug 1;76(3):562-9
references: 2378986
references: Blood. 1999 Sep 15;94(6):1848-54
references: 10477713
references: Proc Natl Acad Sci U S A. 2012 Jun 26;109 (26):10534-9
references: 22689981
references: Nat Commun. 2014 Jun 02;5:3904
references: 24887457
references: Leukemia. 2011 Jul;25(7):1153-8
references: 21415852
references: Nat Genet. 2014 Feb;46(2):166-70
references: 24413734
references: N Engl J Med. 2012 Jan 5;366(1):95-6
references: 22216861
references: EMBO J. 2012 Sep 12;31(18):3704-17
references: 22903061
references: J Clin Oncol. 2009 Aug 20;27(24):3959-63
references: 19620484
references: Nat Med. 1997 Jul;3(7):730-7
references: 9212098
references: J Clin Invest. 2005 Jun;115(6):1636-43
references: 15902303
references: N Engl J Med. 2008 Aug 7;359(6):575-83
references: 18687638
references: J Clin Invest. 2004 Apr;113(7):1008-16
references: 15057307
references: Nature. 2014 Feb 20;506(7488):328-33
references: 24522528
references: Nature. 2011 Jul 27;476(7360):298-303
references: 21796119
references: Br J Haematol. 2007 Dec;139(5):701-8
references: 18021084