title: Prognostic value of telomere attrition in patients with aplastic anemia.
abstract: The decision to pursue hematopoietic stem cell transplantation or immunosuppression as first therapy in severe aplastic anemia is currently based on age and availability of a histocompatible donor. The ability to predict hematologic response, relapse and clonal evolution could improve treatment allocation. In the past 15 years, telomeres have been implicated in clinical diseases such as aplastic anemia, pulmonary fibrosis, cirrhosis and cancer development. The clinical relevance of varying telomere lengths (TL) and/or mutations in genes of the telomerase complex (TERC, TERT) is evolving in aplastic anemia. A large retrospective analysis suggests that baseline TL associate with late events of hematologic relapse and clonal evolution in aplastic anemia patients treated initially with anti-thymocyte globulin-based therapy. Further laboratory experiments propose possible mechanistic insight into genomic instability of bone marrow cells derived from patients with critically short telomeres and/or mutation in telomerase genes. The possibility of modulating telomere attrition rate with sex hormones could positively affect clonal evolution rates in humans. This review will summarize studies in marrow failure that explore the association between telomeres and aplastic anemia outcomes.
authors: Hematology Service, Oncology Center, Hospital São Jose, Beneficência Portuguesa, Rua Martiniano de Carvalho, 951, São Paulo, SP 01321-001, Brazil. phillip.scheinberg@hospitalsjose.org.br
authors: Phillip
authors: P
authors: Scheinberg
mesh_terms: D000741:Anemia, Aplastic / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D011379:Prognosis; D012008:Recurrence; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D019098:Telomerase
references: Leukemia. 2012 Apr;26(4):700-7
references: 22005790
references: Blood. 2002 Aug 15;100(4):1185-91
references: 12149196
references: Int J Hematol. 2006 Aug;84(2):118-22
references: 16926132
references: Blood. 2012 Jan 12;119(2):345-54
references: 22067384
references: JAMA. 2003 Mar 5;289(9):1130-5
references: 12622583
references: Cancer Epidemiol Biomarkers Prev. 2011 Jun;20(6):1238-50
references: 21467229
references: Br J Haematol. 1998 Feb;100(2):393-400
references: 9488634
references: Br J Haematol. 1999 Aug;106(2):377-84
references: 10460594
references: Nat Genet. 2002 Oct;32(2):280-4
references: 12355086
references: Haematologica. 2011 May;96(5):771-4
references: 21273269
references: PLoS One. 2011;6(6):e20466
references: 21695195
references: Br J Haematol. 2009 Jan;144(2):206-16
references: 19036108
references: Blood. 2002 May 1;99(9):3129-35
references: 11964274
references: Blood. 2012 Aug 9;120(6):1185-96
references: 22517900
references: Klin Padiatr. 1998 Jul-Aug;210(4):173-9
references: 9743949
references: Br J Haematol. 2008 Jul;142(3):427-35
references: 18537977
references: Nat Genet. 2003 Feb;33(2):203-7
references: 12539050
references: Br J Haematol. 1982 Aug;51(4):541-50
references: 7049219
references: Pediatr Hematol Oncol. 2009 Oct-Nov;26(7):487-95
references: 19863204
references: Lancet. 2003 Nov 15;362(9396):1628-30
references: 14630445
references: Blood. 2008 May 1;111(9):4446-55
references: 18239083
references: Blood. 2009 Sep 10;114(11):2236-43
references: 19561322
references: Eur J Haematol. 2010 Feb 1;84(2):154-9
references: 19912311
references: Clin Infect Dis. 2011 Mar 15;52(6):726-35
references: 21367725
references: J Immunol. 2002 Jun 15;168(12):5984-8
references: 12055203
references: Ann Hematol. 2012 Jul;91(7):1115-20
references: 22476886
references: Blood. 2000 Mar 15;95(6):1931-4
references: 10706857
references: Br J Haematol. 1987 Mar;65(3):295-300
references: 3567083
references: JAMA. 2010 Jul 7;304(1):69-75
references: 20606151
references: JAMA. 2010 Sep 22;304(12):1358-64
references: 20858879
references: Blood. 2005 Sep 15;106(6):2102-4
references: 15933058
references: Blood. 2001 Feb 15;97(4):895-900
references: 11159514
references: Hematology Am Soc Hematol Educ Program. 2012;2012:292-300
references: 23233595
references: Cell. 2001 Oct 5;107(1):67-77
references: 11595186
references: N Engl J Med. 2005 Apr 7;352(14):1413-24
references: 15814878
references: N Engl J Med. 2012 Jul 5;367(1):11-9
references: 22762314
references: Haematologica. 2011 Sep;96(9):1269-75
references: 21606164
references: J Pediatr. 2008 Dec;153(6):814-9
references: 18672253
references: Blood. 2000 Sep 15;96(6):2049-54
references: 10979946
references: Br J Haematol. 2006 Jun;133(6):622-7
references: 16704436
references: Blood. 2006 Oct 15;108(8):2509-19
references: 16778145
references: Blood. 1998 May 15;91(10):3582-92
references: 9572992
references: N Engl J Med. 2009 Dec 10;361(24):2353-65
references: 20007561
references: N Engl J Med. 2011 Aug 4;365(5):430-8
references: 21812672
references: Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2649-55
references: 18086770