Anemia Fanconi : Article Review
DOI:
https://doi.org/10.53089/medula.v14i2.931Keywords:
Fanconi Anemia, Molecular Biology, Congenital AbnormalitiesAbstract
Fanconi anemia (AF) is a rare, multisystem genetic disorder that affects various physiological aspects, especially the bone marrow, and increases the risk of cancer, such as acute myeloid leukemia (AML) and head and neck cancer. This disease is caused by mutations in 23 genes of the FA/BRCA DNA repair pathway. This article presents the results of a literature study on FA, with a focus on etiology, pathophysiology, molecular pathology, diagnosis, risk factors, clinical symptoms, and management. Through literature study methods, the author collected information from national and international journal sources between 2012 and 2021. The etiology of FA involves mutations in 23 FA genes, with variations in carrier frequency depending on ethnic group. The pathophysiology of FA is related to the inability of cells to repair damaged DNA interstrand crosslinks (ICLs), which can lead to bone marrow failure. Molecular pathology involves the function of the FA/BRCA repair pathway and its impact on the genome. Diagnosis of FA requires clinical evaluation, molecular analysis, and bone marrow examination. Risk factors involve genetic aspects and specific carrier frequencies in ethnic populations. Clinical symptoms of FA involve anemia, infection, and somatic manifestations. Management of FA depends on the severity, with hematopoietic stem cell transplantation (HSCT) being the primary choice. HSCT from matched, nonmatched, or haploidentical donors has provided increasingly better results. This study underscores the importance of early diagnosis of FA to improve prognosis. Although HSCT is the primary treatment option, careful consideration of risks and benefits must be taken. The results of this literature study provide in-depth insight into FA, supporting appropriate monitoring and management efforts for individuals with this condition.
References
Dufour C. How I Manage Patients With Fanconi Anaemia. Br J Haematol. 2017;178(1):32-47.
Svahn J, Bagnasco F, Cappelli E, et al. Somatic, Hematologic Phenotype, Long-Term Outcome, and Effect of Hematopoietic Stem-Cell Transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Associa- tion of Pediatric Hematology-Oncology). Am J Hematol. 2016;91(7):666-671.
Wegman-Ostrosky T, Savage SA. The Genomics of Inherited Bone Marrow Failure: From Mechanism To The Clinic. Br J Haematol. 2017;177(4):526-542.
Ceccaldi R, Sarangi P, D’Andrea AD. The Fanconi Anaemia Pathway: New Players and New Functions. Nat Rev Mol Cell Biol. 2016;17(6):337-349.
Garaycoechea JI, Crossan GP, Langevin F, Daly M, Arends MJ, Patel KJ. Genotoxic Consequences of Endogenous Aldehydes on Mouse Haematopoietic Stem Cell Function. Nature. 2012;489(7417):571-575.
Dufour C, Corcione A, Svahn J, et al. TNF-Alpha And IFN-Gamma are Overexpressed in The Bone Marrow of Fanconi Anemia Patients and TNF-Alpha Suppresses Erythropoiesis In Vitro. Blood. 2003; 102(6):2053-2059.
Zhang H, Kozono DE, O’Connor KW, et al. TGF-Β Inhibition Rescues Hematopoietic Stem Cell Defects and Bone Marrow Failure in Fanconi Anemia. Cell Stem Cell. 2016;18(5):668-681.
Jaber S, Toufektchan E, Lejour V, Bardot B, Toledo F. P53 Downregulates The Fanconi Anaemia DNA Repair Pathway. Nat Commun. 2016;7:11091.
Cappelli E, Cuccarolo P, Stroppiana G, et al. Defects in Mitochondrial Energetic Function Compels Fanconi Anaemia Cells to Glycolytic Metabolism. Biochim Biophys Acta Mol Basis Dis. 2017;1863(6):1214-1221.
Kumari U, Ya Jun W, Huat Bay B, Lyakhovich A. Evidence of Mitochondrial Dysfunction and Impaired ROS Detoxifying Machinery in Fanconi Anemia Cells. Oncogene. 2014;33(2):165-172
Frohnmayer L, Ravenhorst SV, Wirkkula L. Fanconi Anemia Clinical Care Guidelines Fifth Edition. 2020.
Garaycoechea JI, Patel KJ. Why Does The Bone Marrow Fail in Fanconi Anemia?. Blood. 2014; 123(1):26-34.
Nalepa G, Clapp DW. Fanconi Anaemia and Cancer: An Intricate Relationship. Nat Rev Cancer. 2018;18:168–185.
Stone MP, Cho YJ, Huang H, Kim HY, Kozekov ID, Kozekova A, Wang H, Minko IG, Lloyd RS, Harris TM, et al. Interstrand DNA Cross-Links Induced by Alpha, Beta-Unsaturated Aldehydes Derived From Lipid Peroxidation and Environmental Sources. Acc Chem Res. 2008; 41:793–804.
Niraj J, Färkkilä A, D'Andrea AD. The Fanconi Anemia Pathway in Cancer. Annu Rev Cancer Biol. 2019;3:457–478.
Milletti G, Strocchio L, Pagliara D, Girardi K, Carta R, Mastronuzzi A, Locatelli F, Nazio F. Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer Predisposition. Cancers (Basel). 2020;12(2684).
Che R, Zhang J, Nepal M, Han B, Fei P. Multifaceted Fanconi Anemia Signaling. Trends Genet. 2018;34:171–183.
Duxin JP, Walter JC. What is The DNA Repair Defect Underlying Fanconi Anemia? Curr Opin Cell Biol. 2015;37:49–60.
Singh TR, Saro D, Ali AM, Zheng XF, Du CH, Killen MW, Sachpatzidis A, Wahengbam K, Pierce AJ, Xiong Y, et al. MHF1-MHF2, A Histone-fold-containing Protein Complex, Participates in The Fanconi Anemia Pathway Via FANCM. Mol Cell. 2010;37:879–886.
Shakeel S, Rajendra E, Alcón P, O'Reilly F, Chorev DS, Maslen S, Degliesposti G, Russo CJ, He S, Hill CH, et al. Structure of The Fanconi Anaemia Monoubiquitin Ligase Complex. Nature. 2019;575:234–237.
Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER III, Hurov KE, Luo J, Ballif BA, Gygi SP, Hofmann K, D'Andrea AD, et al. Identification of The FANCI Protein, a Monoubiquitinated FANCD2 Paralog Required for DNA Repair. Cell. 2007;129:289–301.
Mehta PA, Davies SM, Leemhuis T, Myers K, Kernan NA, Prockop SE, Scaradavou A, O'Reilly RJ, Williams DA, Lehmann L, et al. Radiation-free, alternative-donor HCT for Fanconi anemia patients: Results from a prospective multi-institutional study. Blood. 2017;129:2308–2315.
Ebens CL, MacMillan ML, Wagner JE. Hematopoietic cell transplantation in Fanconi anemia: Current evidence, challenges and recommendations. Expert Rev Hematol. 2018;10:81–97.
Chandrasekharappa SC, Lach FP, Kimble DC, Kamat A, Teer JK, Donovan FX, Flynn E, Sen SK, Thongthip S, Sanborn E, Smogorzewska A, Auerbach AD, Ostrander EA., Program Pengurutan Komparatif NISC. Teknologi pengurutan paralel besar-besaran, aCGH, dan RNA-Seq memberikan diagnosis molekuler anemia Fanconi yang komprehensif. Oncogene. 121 (22):e138-48
Velleuer E, Carlberg C. Dampak Epigenetika pada Komplikasi Anemia Fanconi: Peran Imunitas Termodulasi Vitamin D. Nutrisi. 09 Mei 2020; 12 (5)
Wang W. Munculnya jaringan respons kerusakan DNA yang terdiri dari anemia Fanconi dan protein BRCA. Nat Rev Genet. Oktober 2007; 8 (10):735-48
Meetei AR, Levitus M, Xue Y, Medhurst AL, Zwaan M, Ling C, Rooimans MA, Bier P, Hoatlin M, Pals G, de Winter JP, Wang W, Joenje H. Warisan terkait X dari kelompok komplementasi anemia Fanconi B .Nat Genet. November 2004; 36 (11):1219-24
Che R, Zhang J, Nepal M, Han B, Fei P. Sinyal Anemia Fanconi Beraneka Ragam. Tren Genet. Maret 2018; 34 (3):171-183
Gulbis B, Eleftheriou A, Angastiniotis M, Ball S, Surrallés J, Castella M, Heimpel H, Hill A, Corrons JL. Epidemiologi anemia langka di Eropa. Adv Exp Med Biol. 2010; 686 :375-96.
Schroeder TM, Tilgen D, Krüger J, Vogel F. Genetika formal anemia Fanconi. Hum Genet. 1976 29 Juni; 32 (3):257-88.
Tip AJ, Pearson T, Morgan NV, Gibson RA, Kuyt LP, Havenga C, Gluckman E, Joenje H, de Ravel T, Jansen S, Mathew CG. Bukti molekuler dan silsilah untuk efek pendiri pada keluarga anemia Fanconi pada populasi Afrikaner di Afrika Selatan. Proc Natl Acad Sci US A. 2001 Mei 08; 98 (10):5734-9
Rosenberg PS, Tamary H, Ubah BP. Seberapa tinggi frekuensi pembawa sindrom resesif yang langka? Perkiraan kontemporer untuk Anemia Fanconi di Amerika Serikat dan Israel. Am J Med Genet A. 2011 Agustus; 155A (8):1877-83
Aljurf, M. D., Gluckman, E., & Dufour, C. (2017). Congenital and Acquired Bone Marrow Failure. In Congenital and Acquired Bone Marrow Failure. Elsevier.
Bhandari, J., Thada, P. K., & Puckett., Y. (2022). Fanconi Anemia. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK559133/
Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after fifteen years of follow-up. Haematologica. 2018;103(1):30-39.
Choijilsuren HB, Park Y, Jung M. Mechanisms of somatic transformation in inherited bone marrow failure syndromes. Hematology Am Soc Hematol Educ Program. 2021;2021(1):390-398.
Ayas M, Saber W, Davies SM, et al. Allogeneic hematopoietic cell transplan- tation for Fanconi anemia in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome, or acute leukemia. J Clin Oncol. 2013;31(13):1669-1676.
Peffault de Latour R, Soulier J. How I treat MDS and AML in Fanconi anemia. Blood. 2016;127(24):2971-2979.
Tönnies H, Huber S, Kuhl J-S, Gerlach A, Ebell W, Neitzel H. Clonal chromo- somal aberrations in bone marrow cells of Fanconi anemia patients: gains of the chromosomal segment 3q26q29 as an adverse risk factor. Blood. 2003; 101(10):3872-3874.
Meyer S, Bristow C, Wappett M, et al. Fanconi anemia (FA)-associated 3q gains in leukemic transformation consistently target EVI1, but do not affect low TERC expression in FA. Blood. 2011;117(22):6047-6050.
Quentin S, Cuccuini W, Ceccaldi R, et al. Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnor- malities that includes cryptic RUNX1/AML1 lesions. Blood. 2011;117(15): e161-e170.
Giardino S, de Latour RP, Aljurf M, et al; Severe Aplastic Anemia and Chronic Malignancies Working Parties of European Blood and Marrow Transplanta- tion Group. Outcome of patients with Fanconi anemia developing myel- odysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: a retrospective analysis on behalf of EBMT group. Am J Hematol. 2020;95(7):809-816.
Debureaux PE, Sicre de Fontbrune F, Bonfim C, et al. FLAG-sequential regimen followed by bone marrow transplantation for myelodysplastic syndrome or acute leukemia in patients with Fanconi anemia: a Franco- Brazilian study. Bone Marrow Transplant. 2021;56(1):285-288.
Peffault de Latour R, Porcher R, Dalle J-H, et al; AF Committee of the Severe Aplastic Anemia Working Party; Pediatric Working Party of the European Group for Blood and Marrow Transplantation. Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: the European Group for Blood and Marrow Transplantation experience. Blood. 2013;122(26):4279-4286.
Rosenberg PS, Socié G, Alter BP, Gluckman E. Risk of head and neck squa- mous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants. Blood. 2005;105(1):67-73.
Diaz De Heredia C, Bierings M, Dalle JH, et al. Fanconi’s anemia and other hereditary bone marrow failure syndromes. In: Carreras E, Dufour C, Mohty M, et al, eds. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. 7th ed. Cham, Switzerland: Springer; 2019: 587.
Alter BP. Fanconi anemia and the development of leukemia. Best Pract Res Clin Haematol. 2014;27(3-4):214-221.
Ebens CL, MacMillan ML, Wagner JE. Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations. Expert Rev Hematol. 2017; 10(1):81-97.
Giardino S, Bagnasco F, Falco M, et al. Haploidentical stem cell transplan- tation after TCR-αβ+ and CD19+ cells depletion in children with congenital non-malignant disease. Transplant Cell Ther. 2022; 28(7): 394. e1-394394.e9.
Reisner Y, Hagin D, Martelli MF. Haploidentical hematopoietic transplanta- tion: current status and future perspectives. Blood. 2011;118(23):6006-6017.
Strocchio L, Pagliara D, Algeri M, et al. HLA-haploidentical TCRαβ+/ CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia. Blood Adv. 2021;5(5):1333-1339.
Bonfim C, Nichele S, Loth G, et al. Transplantation for Fanconi anaemia: lessons learned from Brazil. Lancet Haematol. 2022; 9(3): e228-e236.
Zubicaray J, Pagliara D, Sevilla J, et al. Haplo-identical or mismatched unre- lated donor hematopoietic cell transplantation for Fanconi anemia: results from the Severe Aplastic Anemia Working Party of the EBMT. Am J Hematol. 2021;96(5):571-579.
Calado RT, Clé DV. Treatment of inherited bone marrow failure syndromes beyond transplantation. Hematology Am Soc Hematol Educ Program. 2017;2017(1):96-101.
Pollard JA, Furutani E, Liu S, et al. Metformin for treatment of cytope- nias in children and young adults with Fanconi anemia. Blood Adv. 2022;6(12):3803-3811.
Mehta PA, Fukuda T, Zhao J, et al. Quercetin: a novel targeted chemo- prevention for patients with Fanconi anemia (FA). Blood. 2017;130(suppl 1):1178.
Scheinberg P. Activity of eltrombopag in severe aplastic anemia. Hematol- ogy Am Soc Hematol Educ Program. 2018(1):450-456.
Peffault de Latour R, Kulasekararaj A, Iacobelli S, et al; Severe Aplastic Ane- mia Working Party of the European Society for Blood and Marrow Trans- plantation. Eltrombopag added to immunosuppression in severe aplastic anemia. N Engl J Med. 2022; 386 (1): 11-23.
Guenther KL, Cheruku PS, Cash A, et al. Eltrombopag promotes DNA repair in human hematopoietic stem and progenitor cells. Exp Hematol. 2019;73:1-6.e66e6.
Barranta ME, Chinian F, Roskom K, et al. Prospective phase I/II study of eltrombopag for the treatment of bone marrow failure in Fanconi anemia. Poster session presented at: 508. Bone Marrow Failure: Poster II, 63th ASH Annual Meeting and Exposition; 2021 December 11-14; Atlanta, GA.
Sevilla J, Navarro S, Rio P, et al. Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy pur- poses. Mol Ther Methods Clin Dev. 2021;22:66-75.
Pierri F, Faraci M, Giardino S, Dufour C. Hematopoietic stem cell transplan- tation for classical inherited bone marrow failure syndromes: an update. Expert Rev Hematol. 2021;14(10):911-925.
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