title: Hematopoietic stem cell aging and chronic lymphocytic leukemia pathogenesis.
abstract: Human malignancies develop through the multistep acquisition of critical somatic mutations during the clinical course. Regarding hematological malignancies, 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 and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are considered to directly originate from differentiated mature lymphocytes; however, we previously reported that the propensity to generate clonal B cells had already been acquired at the HSC stage in CLL patients. Similarly, HSC involvement has been reported in the pathogenesis of mature T cell lymphomas. These studies indicate that, in mature lymphoid, if not all, malignancies, HSCs should be considered as the critical cellular target in the oncogenic process. The prevalence of these hematological malignancies dramatically increases with age, and the effect of aging HSCs should thus be taken into account when investigating the stepwise malignant transformation process of these age-associated malignancies.
authors.affiliation: Department of Medicine and Biosystemic Sciences, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
authors.forename: Yoshikane
authors.initials: Y
authors.lastname: Kikushige
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D016922:Cellular Senescence; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
references.citation: Leukemia. 2010 Jan;24(1):133-40
references.pmid: 19946263
references.citation: Semin Immunol. 2012 Oct;24(5):309-20
references.pmid: 22559987
references.citation: Nature. 2010 Mar 25;464(7288):520-8
references.pmid: 20336134
references.citation: J Exp Med. 2004 Aug 16;200(4):411-23
references.pmid: 15314072
references.citation: Blood. 2001 Oct 1;98(7):2043-51
references.pmid: 11567988
references.citation: J Clin Invest. 2005 Jun;115(6):1636-43
references.pmid: 15902303
references.citation: Nature. 2012 Sep 13;489(7415):309-12
references.pmid: 22885698
references.citation: Cell. 2007 Jun 15;129(6):1097-110
references.pmid: 17574023
references.citation: J Immunol. 2003 Sep 1;171(5):2326-30
references.pmid: 12928378
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20012-7
references.pmid: 22123971
references.citation: J Exp Med. 2001 Dec 3;194(11):1625-38
references.pmid: 11733577
references.citation: N Engl J Med. 2005 Feb 24;352(8):804-15
references.pmid: 15728813
references.citation: N Engl J Med. 2008 Aug 7;359(6):575-83
references.pmid: 18687638
references.citation: Biol Blood Marrow Transplant. 2012 Jan;18(1 Suppl):S40-5
references.pmid: 22226111
references.citation: Blood. 2007 Dec 15;110(13):4576-83
references.pmid: 17785583
references.citation: N Engl J Med. 2009 Feb 12;360(7):659-67
references.pmid: 19213679
references.citation: N Engl J Med. 2011 Dec 29;365(26):2497-506
references.pmid: 22150006
references.citation: Cell. 2008 Feb 22;132(4):681-96
references.pmid: 18295583
references.citation: Nat Med. 1996 Sep;2(9):1011-6
references.pmid: 8782459
references.citation: J Exp Med. 2012 Nov 19;209(12):2183-98
references.pmid: 23091163
references.citation: J Exp Med. 2011 Dec 19;208(13):2691-703
references.pmid: 22110168
references.citation: Blood. 2009 Jul 2;114(1):33-7
references.pmid: 19420353
references.citation: Cell. 2012 Jul 20;150(2):264-78
references.pmid: 22817890
references.citation: Cell Stem Cell. 2013 Apr 4;12(4):413-25
references.pmid: 23415915
references.citation: Leuk Res. 2009 Mar;33(3):368-76
references.pmid: 18640719
references.citation: Cancer Cell. 2011 Aug 16;20(2):246-59
references.pmid: 21840488
references.citation: Blood. 2004 Jun 15;103(12):4389-95
references.pmid: 14962897
references.citation: Sci Transl Med. 2012 Aug 29;4(149):149ra118
references.pmid: 22932223
references.citation: Stem Cells Transl Med. 2012 Sep;1(9):651-7
references.pmid: 23197871
references.citation: J Exp Med. 2000 Nov 6;192(9):1273-80
references.pmid: 11067876
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7521-6
references.pmid: 10861016
references.citation: Blood. 2003 Oct 15;102(8):2994-3002
references.pmid: 12829608
references.citation: Nat Genet. 2014 Feb;46(2):171-5
references.pmid: 24413737
references.citation: Br J Haematol. 2005 Aug;130(3):325-32
references.pmid: 16042682
references.citation: Curr Opin Hematol. 2013 Jul;20(4):355-61
references.pmid: 23739721
references.citation: Blood. 2009 Jul 2;114(1):26-32
references.pmid: 19029437
references.citation: Br J Haematol. 2007 Dec;139(5):701-8
references.pmid: 18021084
references.citation: Nat Immunol. 2004 Feb;5(2):133-9
references.pmid: 14749784
references.citation: Nature. 2014 Feb 13;506(7487):240-4
references.pmid: 24429522
references.citation: Blood. 2014 Feb 27;123(9):1319-26
references.pmid: 24345750
references.citation: Semin Oncol. 2004 Apr;31(2):185-97
references.pmid: 15112149
references.citation: N Engl J Med. 2012 Mar 22;366(12):1090-8
references.pmid: 22417201
references.citation: Cytometry B Clin Cytom. 2003 Mar;52(1):1-12
references.pmid: 12599176
references.citation: Nature. 2010 Apr 8;464(7290):852-7
references.pmid: 20305640
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9194-9
references.pmid: 15967997
references.citation: Nature. 2011 Sep 11;478(7367):64-9
references.pmid: 21909114
references.citation: Cytometry B Clin Cytom. 2007 Sep;72(5):344-53
references.pmid: 17266153
references.citation: J Clin Oncol. 2008 Sep 20;26(27):4497-503
references.pmid: 18662968
references.citation: Nature. 2014 Feb 20;506(7488):328-33
references.pmid: 24522528
references.citation: Nature. 2011 Jun 05;475(7354):101-5
references.pmid: 21642962
references.citation: J Clin Oncol. 2009 Aug 20;27(24):3959-63
references.pmid: 19620484
references.citation: Am J Med. 2004 Apr 5;116 Suppl 7A:3S-10S
references.pmid: 15050882
references.citation: Aging Cell. 2011 Jun;10(3):542-6
references.pmid: 21418508
references.citation: J Immunol. 2006 Jan 15;176(2):1007-12
references.pmid: 16393987
references.citation: Cancer Cell. 2011 Jul 12;20(1):25-38
references.pmid: 21723201
references.citation: Br J Haematol. 2007 Dec;139(5):832-6
references.pmid: 17961190
references.citation: Int J Hematol. 2005 Dec;82(5):371-6
references.pmid: 16533737
references.citation: Blood. 2012 Sep 27;120(13):2589-99
references.pmid: 22665934
references.citation: Nat Genet. 2011 Dec 11;44(1):47-52
references.pmid: 22158541
references.citation: Nature. 2007 Jun 7;447(7145):686-90
references.pmid: 17554302
references.citation: Nat Rev Cancer. 2010 Jan;10(1):37-50
references.pmid: 19956173
references.citation: Blood. 2011 Sep 15;118(11):2941-50
references.pmid: 21734240
references.citation: Leukemia. 2011 Jul;25(7):1153-8
references.pmid: 21415852
references.citation: J Exp Med. 2001 Dec 3;194(11):1639-47
references.pmid: 11733578
references.citation: Trends Immunol. 2005 Aug;26(8):426-33
references.pmid: 15979407
references.citation: Blood. 2004 Oct 15;104(8):2499-504
references.pmid: 15217828
references.citation: Blood. 2013 Jan 31;121(5):840-8
references.pmid: 23233661
references.citation: Blood. 2007 Jan 1;109(1):259-70
references.pmid: 16985177
references.citation: Blood. 1999 Sep 15;94(6):1848-54
references.pmid: 10477713
references.citation: Nature. 2012 Jan 11;481(7382):506-10
references.pmid: 22237025