Seminars in Hematology
Volume 43, Issue 3 , Pages 147-156 , July 2006

Fanconi Anemia

  • Grover C. Bagby

      Affiliations

    • OHSU Cancer Institute, Departments of Medicine and Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR.
    • Corresponding Author InformationAddress correspondence to Grover C. Bagby, MD, OHSU Cancer Institute, CR145, 3181 SW Sam Jackson Park Rd, Portland, OR 97239.
    • ,
  • Blanche P. Alter

      Affiliations

    • Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.

References 

  1. Fanconi G . Familiare infantile perniziosaartige anaemia (pernizioses blutbild und konstitution) . Jahrb Kinderhilkd . 1927;117:257–280
  2. Joenje H , Patel KJ . The emerging genetic and molecular basis of Fanconi anaemia . Nat Rev Genet . 2001;2:446–459
  3. Alter BP . Inherited bone marrow failure syndromes . In:  Nathan DG ,  Orkin SH ,  Ginsburg D ,  Look AT editor. Hematology of Infancy and Childhood . Philadelphia, PA: Saunders; 2003;p. 280–365
  4. Kutler DI , Singh B , Satagopan J , Batish SD , Berwick M , Giampietro PF , et al.  A 20-year perspective on the International Fanconi Anemia Registry (IFAR) . Blood . 2003;101:1249–1256
  5. Sasaki MS , Tonomura A . A high susceptibility of Fanconi’s anemia to chromosome breakage by DNA cross-linking agents . Cancer Res . 1973;33:1829–1836
  6. Auerbach AD , Adler B , Chaganti RS . Prenatal and postnatal diagnosis and carrier detection of Fanconi anemia by a cytogenetic method . Pediatrics . 1981;67:128–135
  7. Meetei AR , Levitus M , Xue Y , Medhurst AL , Zwaan M , Ling C , et al.  X-linked inheritance of Fanconi anemia complementation group B . Nat Genet . 2004;36:1219–1224
  8. Levitus M , Waisfisz Q , Godthelp BC , Vries YD , Hussain S , Wiegant WW , et al.  The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J . Nat Genet . 2005;37:934–935
  9. Levran O , Attwooll C , Henry RT , Milton KL , Neveling K , Rio P , et al.  The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia . Nat Genet . 2005;37:931–933
  10. Meetei AR , de Winter JP , Medhurst AL , Wallisch M , Waisfisz Q , van de Vrugt HJ , et al.  A novel ubiquitin ligase is deficient in Fanconi anemia . Nat Genet . 2003;35:165–170
  11. Bagby GC . Genetic basis of Fanconi anemia . Curr Opin Hematol . 2003;10:68–76
  12. Howlett NG , Taniguchi T , Olson S , Cox B , Waisfisz Q , Die-Smulders C , et al.  Biallelic inactivation of BRCA2 in Fanconi anemia . Science . 2002;297:606–609
  13. Garcia-Higuera I , Kuang Y , Naf D , Wasik J , D’Andrea AD . Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex . Mol Cell Biol . 1999;19:4866–4873
  14. Garcia-Higuera I , Taniguchi T , Ganesan S , Meyn MS , Timmers C , Hejna J . Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway . Mol Cell . 2001;7:249–262
  15. Medhurst AL , Huber PA , Waisfisz Q , de Winter J , Mathew CG . Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway . Hum Mol Genet . 2001;10:423–429
  16. Pang Q , Fagerlie S , Christianson TA , Keeble W , Faulkner G , Diaz J , et al.  The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors . Mol Cell Biol . 2000;20:4724–4735
  17. Pang Q , Keeble W , Christianson TA , Faulkner G , Bagby GC . FANCC interacts with hsp70 to protect hematopoietic cells from IFNγ/TNFα-mediated cytotoxicity . EMBO J . 2001;20:4478–4489
  18. Pang QS , Christianson TA , Keeble W , Koretsky T , Bagby GC . The anti-apoptotic function of Hsp70 in the interferon-inducible double-stranded RNA-dependent protein kinase-mediated death signaling pathway requires the Fanconi anemia protein, FANCC . J Biol Chem . 2002;277:49638–49643
  19. Fagerlie S , Lensch MW , Pang Q , Bagby GC  The Fanconi anemia group C gene product . Signaling functions in hematopoietic cells . Exp Hematol . 2001;29:1371–1381
  20. Sobeck A , Stone S , Costanzo V , de Graaf B , Reuter T , de Winter J , et al.  Fanconi anemia proteins are required to prevent accumulation of replication-associated DNA double-strand breaks . Mol Cell Biol . 2006;26:425–437
  21. Kupfer GM , Näf D , Suliman A , Pulsipher M , D’Andrea AD . The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex . Nat Genet . 1997;17:487–490
  22. Näf D , Kupfer GM , Suliman A , Lambert K , D’Andrea AD . Functional activity of the Fanconi anemia protein FAA requires FAC binding and nuclear localization . Mol Cell Biol . 1998;18:5952–5960
  23. Hoatlin ME , Christianson TA , Keeble WW , Hammond AT , Zhi Y , Heinrich MC , et al.  The Fanconi anemia group C gene product is located in both the nucleus and cytoplasm of human cells . Blood . 1998;91:1418–1425
  24. Thomashevski A , High AA , Drozd M , Shabanowitz J , Hunt DF , Grant PA , et al.  The Fanconi anemia core complex forms 4 different sized complexes in different subcellular compartments . J Biol Chem . 2004;79:26201–26209
  25. Godthelp BC , Artwert F , Joenje H , Zdienicka MZ . Impaired DNA damage-induced nuclear Rad51 foci formation uniquely characterizes Fanconi anemia group D1 . Oncogene . 2002;21:5002–5005
  26. Xia F , Taghian DG , DeFrank JS , Zeng ZC , Willers H , Iliakis G , et al.  Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining . Proc Natl Acad Sci U S A . 2001;98:8644–8649
  27. Davies AA , Masson J , McIlwraith MJ , Stasiak AZ , Stasiak A , Venkitaraman AR , et al.  Role of BRCA2 in control of the RAD51 recombination and DNA repair protein . Mol Cell . 2001;7:273–282
  28. Gowen LC , Avrutskaya AV , Latour AM , Koller BH , Leadon SA . BRCA1 required for transcription-coupled repair of oxidative DNA damage . Science . 1998;281:1009–1012
  29. Moynahan ME , Pierce AJ , Jasin M . BRCA2 is required for homology-directed repair of chromosomal breaks . Mol Cell . 2001;7:263–272
  30. Aprelikova O , Pace AJ , Fang B , Koller BH , Liu ET . BRCA1 is a selective co-activator of 14-3-3 sigma gene transcription in mouse embryonic stem cells . J Biol Chem . 2001;276:25647–25650
  31. Siddique H , Zou JP , Rao VN , Reddy ESP . The BRCA2 is a histone acetyltransferase . Oncogene . 1998;16:2283–2285
  32. Yarden RI , Brody LC . BRCA1 interacts with components of the histone deacetylase complex . Proc Natl Acad Sci U S A . 1999;96:4983–4988
  33. Zhang HB , Somasundaram K , Peng Y , Tian H , Zhang HX , Bi DK , et al.  BRCA1 physically associates with p53 and stimulates its transcriptional activity . Oncogene . 1998;16:1713–1721
  34. Gao B , Shen XN , Kunos G , Meng QH , Goldberg ID , Rosen EM , et al.  Constitutive activation of JAK-STAT3 signaling by BRCA1 in human prostate cancer cells . FEBS Lett . 2001;488:179–184
  35. Kubista M , Rosner M , Kubista E , Bernaschek G , Hengstschlager M . Brca1 regulates in vitro differentiation of mammary epithelial cells . Oncogene . 2002;21:4747–4756
  36. Zheng L , Li S , Boyer TG , Lee WH . Lessons learned from BRCA1 and BRCA2 . Oncogene . 2000;19:6159–6175
  37. Nadler JJ , Braun RE . Fanconi anemia complementation group C is required for proliferation of murine primordial germ cells . Genesis . 2000;27:117–123
  38. Koomen M , Cheng NC , van de Vrugt HJ , Godthelp BC , Der Valk MA , Oostra AB , et al.  Reduced fertility and hypersensitivity to mitomycin C characterize Fancg/Xrcc9 null mice . Hum Mol Genet . 2002;11:273–281
  39. Cheng NC , van de Vrugt HJ , Van der Valk MA , Oostra AB , Krimpenfort B , de Vries Y , et al.  Mice with a targeted disruption of the Fanconi anemia homolog Fanca . Hum Mol Genet . 2000;9:1805–1811
  40. Rathbun RK , Faulkner GR , Ostroski MH , Christianson T , Hughes G , Jones G , et al.  Inactivation of the Fanconi anemia group C (FAC) gene augments interferon-gamma-induced apoptotic responses in hematopoietic cells . Blood . 1997;90:974–985
  41. Fagerlie SR , Koretsky T , Torok-Storb B , Bagby GC . Impaired type-I IFN-induced Jak/STAT signaling in FA-C cells and abnormal CD4+ Th cell subsets in Fancc-/- mice . J Immunol . 2004;173:3863–3870
  42. Beere HM , Wolf BB , Cain K , Mosser DD , Mahboubi A , Kuwana T , et al.  Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome . Nat Cell Biol . 2000;2:469–475
  43. Beere HM , Green DR . Stress management–Heat shock protein-70 and the regulation of apoptosis . Trends Cell Biol . 2001;11:6–10
  44. Jaattela M , Wissing D , Kokholm K , Kalunki T , Egeblad M . Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteases . EMBO J . 1998;17:6124–6134
  45. Williams BR . PKR; a sentinel kinase for cellular stress . Oncogene . 1999;18:6112–6120
  46. Pang Q , Keeble W , Diaz J , Christianson T , Fagerlie S , Rathbun K , et al.  Role of double-stranded RNA-dependent protein kinase in mediating hypersensitivity of Fanconi anemia complementation group C cells to interferon gamma, tumor necrosis factor-alpha, and double-stranded RNA . Blood . 2001;97:1644–1652
  47. Pagano G . Mitomycin C and diepoxybutane action mechanisms and FANCC protein functions (Further insights into the role for oxidative stress in Fanconi’s anaemia phenotype) . Carcinogenesis . 2000;21:1067–1068
  48. Clarke AA , Philpott NJ , Gordon-Smith EC , Rutherford TR . The sensitivity of Fanconi anaemia group C cells to apoptosis induced by mitomycin C is due to oxygen radical generation, not DNA crosslinking . Br J Haematol . 1997;96:240–247
  49. Cumming RC , Lightfoot J , Beard K , Youssoufian H , O’Brien PJ , Buchwald M . Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1 . Nat Med . 2001;7:814–820
  50. Pang Q , Christianson TA , Keeble W , Diaz J , Faulkner G , Reifsteck C , et al.  The Fanconi anemia complementation group C gene product (structural evidence of multifunctionality) . Blood . 2001;98:1392–1401
  51. Yamashita T , Wu N , Kupfer G , Corless C , Joenje H , Grompe M , et al.  Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity . Blood . 1996;87:4424–4432
  52. Rosenberg PS , Huang Y , Alter BP . Individualized risks of first adverse events in patients with Fanconi anemia . Blood . 2004;104:350–355
  53. Verlander PC , Lin JD , Udono MU , Zhang Q , Gibson RA , Mathew CG , et al.  Mutation analysis of the Fanconi anemia gene FACC . Am J Hum Genet . 1994;54:595–601
  54. Futaki M , Yamashita T , Yagasaki H , Toda T , Yabe M , Kato S , et al.  The IVS4+4 A to T mutation of the Fanconi anemia gene FANCC is not associated with a severe phenotype in Japanese patients . Blood . 2000;95:1493–1498
  55. Faivre L , Guardiola P , Lewis CM , Dokal I , Ebell W , Zatterale A , et al.  Association of complementation group and mutation type with clinical outcome in Fanconi anemia . Blood . 2000;96:4064–4070
  56. Alter BP . Cancer in Fanconi anemia, 1927-2001 . Cancer . 2003;97:425–440
  57. Mankad A , Taniguchi T , Cox B , Akkari Y , Rathbun RK , Lucas L , et al.  Natural gene therapy in monozygotic twins with Fanconi anemia . Blood . 2006;107:3084–3090
  58. Gregory JJ , Wagner JE , Verlander PC , Levran O , Batish SD , Eide CR , et al.  Somatic mosaicism in Fanconi anemia (Evidence of genotypic reversion in lymphohematopoietic stem cells) . Proc Natl Acad Sci U S A . 2001;98:2532–2537
  59. Alter BP , Joenje H , Oostra AB , Pals G . Fanconi anemia (Adult head and neck cancer and hematopoietic mosaicism) . Arch Otolaryngol Head Neck Surg . 2005;131:635–639
  60. Shimamura A , Montes DO , Svenson JL , Haining N , Moreau LA , Nathan DG , et al.  A novel diagnostic screen for defects in the Fanconi anemia pathway . Blood . 2002;100:4649–4654
  61. Hanenberg H , Batish SD , Pollok KE , Vieten L , Verlander PC , Leurs C , et al.  Phenotypic correction of primary Fanconi anemia T cells with retroviral vectors as a diagnostic tool . Exp Hematol . 2002;30:410–420
  62. Chandra S , Levran O , Jurickova I , Maas C , Kapur R , Schindler D , et al.  A Rapid method for retrovirus-mediated identification of complementation groups in Fanconi anemia patients . Mol Ther . 2005;12:976–984
  63. Giampietro PF , Auerbach AD , Elias ER , Gutman A , Zellers NJ , Davis JG . New recessive syndrome characterized by increased chromosomal breakage and several findings which overlap with Fanconi anemia . Am J Med Genet . 1998;78:70–75
  64. Vlachos A , Lipton JM . Hematopoietic stem cell transplant for inherited bone marrow failure syndromes . In:  Mehta P editors. Pediatric Stem Cell Transplantation . Sudbury, MA: Jones and Barlett; 2004;p. 281–311
  65. Grewal SS , Kahn JP , MacMillan ML , Ramsay NKC , Wanger JE . Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype-identical sibling selected using preimplantation genetic diagnosis . Blood . 2004;103:1147–1151
  66. Gluckman E . Radiosensitivity in Fanconi anemia (Application to the conditioning for bone marrow transplantation) . Radiother Oncol . 1990;18(suppl 1):88–93
  67. Alter BP . Fanconi’s anemia, transplantation, and cancer . Pediatr Transplant . 2005;9(suppl 7):81–86
  68. Boyer MW , Gross TG , Loechelt B , Leehuis T , Filipovich A , Harris RE . Low risk of graft-versus-host disease with transplantation of CD34 selected peripheral blood progenitor cells from alternative donors for Fanconi anemia . J Pediatr Hematol Oncol . 2003;25:890–895
  69. Velazquez I , Alter BP . Androgens and liver tumors (Fanconi’s anemia and non-Fanconi’s conditions) . Am J Hematol . 2004;77:257–267
  70. Li X , Yang Y , Yuan J , Hong P , Freie B , Orazi A , et al.  Continuous in vivo infusion of Interferon-gamma (IFN-{gamma}) preferentially reduces myeloid progenitor numbers and enhances engraftment of syngeneic wildtype cells in Fancc-/- mice . Blood . 2004;104:1204–1209
  71. Rosenberg PS , Greene MH , Alter BP . Cancer incidence in persons with Fanconi anemia . Blood . 2003;101:822–826
  72. Rosenberg PS , Socie G , Alter BP , Gluckman E . Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants . Blood . 2005;105:67–73
  73. Alter BP . Radiosensitivity in Fanconi’s anemia patients . Radiother Oncol . 2002;62:345–347
  74. Herrero R , Hildesheim A , Bratti C , Sherman ME , Hutchinson M , Morales J , et al.  Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica . J Natl Cancer Inst . 2000;92:464–474
  75. Gillison ML , Shah KV . Chapter 9 (Role of mucosal human papillomavirus in nongenital cancers) . J Natl Cancer Inst Monogr . 2003;31:57–65
  76. Kutler DI , Wreesmann VB , Goberdhan A , Ben Porat L , Satagopan J , Ngai I , et al.  Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients . J Natl Cancer Inst . 2003;95:1718–1721
  77. van Zeeburg HJ , Snijders PJ , Joenje H , Barkenhoff RH . Re (Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients) . J Natl Cancer Inst . 2004;96:968–969
  78. Fagerlie SR , Bagby GC . Immune defects in Fanconi anemia . Crit Rev Immunol . 2006;26:81–96
  79. Carreau M , Gan OI , Liu L , Doedens M , McKerlie C , Dick JE , et al.  Bone marrow failure in the Fanconi anemia group C mouse model after DNA damage . Blood . 1998;91:2737–2744
  80. Otsuki T , Wang J , Demuth I , Digweed M , Liu JM . Assessment of mitomycin C sensitivity in Fanconi anemia complementation group C gene (Fac) knock-out mouse cells . Int J Hematol . 1998;67:243–248
  81. Alter BP , Caruso JP , Drachtman RA , Uchida T , Velagaleti GVN , Elghetany MT . Fanconi anemia (Myelodysplasia as a predictor of outcome) . Cancer Genet Cytogenet . 2000;117:125–131
  82. Lensch MW , Rathbun RK , Olson SB , Jones GR , Bagby GC . Selective pressure as an essential force in molecular evolution of myeloid leukemic clones (A view from the window of Fanconi anemia) . Leukemia . 1999;13:1784–1789
  83. Rubin CM , Arthur DC , Woods WG , Lange BJ , Nowell PC , Rowley JD , et al.  Therapy-related myelodysplastic syndrome and acute myeloid leukemia in children (Correlation between chromosomal abnormalities and prior therapy) . Blood . 1991;78:2982–2988
  84. Whang-Peng J , Young RC , Lee EC , Longo DL , Schecter GC , DeVita VT . Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities . Blood . 1988;71:403–414
  85. Luna-Fineman S , Shannon KM , Lange BJ . Childhood monosomy 7 (Epidemiology, biology, and mechanistic implications) . Blood . 1995;85:1985–1999
  86. Marmorstein LY , Ouchi T , Aaronson SA . The BRCA2 gene product functionally interacts with p53 and RAD51 . Proc Natl Acad Sci U S A . 1998;95:13869–13874

 Supported in part by grants from the National Heart Lung and Blood Institute, the Department of Veteran’s Affairs, and the Fanconi Anemia Research Fund (G.C.B.). Supported in part by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute (B.P.A.).

PII: S0037-1963(06)00079-5

doi: 10.1053/j.seminhematol.2006.04.005

Seminars in Hematology
Volume 43, Issue 3 , Pages 147-156 , July 2006

Article Tools

* Image Usage & Resolution