Fanconi Anemia (Fanconi's Anemia)

Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004)

Also Known As:

Networked: 1866 relevant articles (36 outcomes, 90 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Aplastic Anemia (Anemia, Hypoplastic)
2.	Leukemia
3.	Bone Marrow Failure Disorders
4.	Congenital Bone Marrow Failure Syndromes
5.	Pancytopenia

Experts

1.	D'Andrea, Alan D: 51 articles (01/2020 - 05/2002)
2.	Schindler, Detlev: 30 articles (01/2022 - 04/2002)
3.	Joenje, Hans: 30 articles (11/2015 - 07/2002)
4.	Takata, Minoru: 27 articles (10/2021 - 08/2003)
5.	Hanenberg, Helmut: 26 articles (01/2022 - 02/2003)
6.	Auerbach, Arleen D: 25 articles (01/2020 - 02/2003)
7.	Pang, Qishen: 21 articles (11/2019 - 12/2002)
8.	Wagner, John E: 21 articles (01/2018 - 01/2004)
9.	de Winter, Johan P: 21 articles (02/2015 - 10/2003)
10.	Surrallés, Jordi: 19 articles (01/2022 - 03/2007)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Fanconi Anemia:

1.	fludarabineIBA 02/01/2010 - "Recent progress has been made, as best evidenced in studies adding fludarabine to the preparative regimen for children undergoing unrelated donor HSCT for Fanconi anemia. " 06/01/2021 - "Bone marrow transplant using fludarabine-based reduced intensity conditioning regimen with in vivo T cell depletion in patients with Fanconi anemia." 04/01/2014 - "We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given T cell-depleted, CD34(+) positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. " 02/01/2010 - "Successful allo-SCT in a Fanconi anemia patient with renal impairment using reduced doses of CY and fludarabine." 07/01/2006 - "In conclusion, fludarabine-based preparative protocols are well tolerated, facilitate rapid engraftment with minimal toxicity, and should be considered an essential component of choice for patients with Fanconi anemia."
2.	DNA (Deoxyribonucleic Acid)IBA 03/01/2003 - "That alphaSpIISigma* is essential for this re-localization is demonstrated by the finding that in cells from patients with Fanconi anemia complementation group A (FA-A), which have decreased ability to repair DNA interstrand cross-links and decreased levels of alphaSpIISigma*, there is a significant reduction in formation of damage-induced XPF as well as alphaSpIISigma* nuclear foci, even though levels of XPF are normal in these cells. " 05/01/2010 - "The aim of this study was to evaluate whether measuring repair kinetics of radiation-induced DNA double-strand breaks (DSBs) can distinguish Fanconi anemia from other BMF patients. " 12/01/1997 - "Conventional subtraction library techniques or DNA-transfection studies are standard techniques applied for identification and isolation of genes relevant in monogenetic diseases like Fanconi anemia (FA). " 10/01/1982 - "In order to develop the usefulness of Fanconi's anemia (FA) lymphoblast lines for biochemical and genetic studies, we have determined their sensitivity to a variety of DNA-damaging chemicals. " 11/01/1977 - "Study of ultraviolet repair & spontaneous DNA strand breaks in Fanconi's anemia cells."
3.	Cyclophosphamide (Cytoxan)FDA LinkGeneric 02/15/2016 - "Furthermore, both XPA and FANCD2 deficient cells were sensitized to PM treatment as compared to that of wild type cells, suggesting that Fanconi anemia and nucleotide excision repair pathways are involved in the removal of cyclophosphamide-induced DNA damage. " 09/01/2005 - "We determined historical adverse event rates from long-term follow-up of 117 Fanconi anemia patients in the Hôpital Saint Louis transplant cohort, who received low-dose cyclophosphamide- and irradiation-based conditioning, in combination with other modalities, between 1976 and October 2002. " 10/01/1993 - "Since 1976, patients grafted at the Hôpital Saint-Louis for Fanconi anemia (FA) without evidence of leukemic transformation have been given a uniform conditioning regimen that consisted of low-dose cyclophosphamide (Cy) and thoracoabdominal irradiation (TAI). " 01/01/1990 - "A male patient with Fanconi anemia (FA) was conditioned with a modified regimen of cyclophosphamide and irradiation that accommodates the abnormally high sensitivity to these agents that is characteristic of FA. " 12/01/1988 - "Patients with Fanconi's anemia require a reduced conditioning program with cyclophosphamide and irradiation for BMT. "
4.	Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)IBA 07/01/1995 - "In the Fanconi's anemia trial, 6 of 7 patients showed some improvement when treated with GM-CSF. " 12/01/2005 - "Overexpression of NPM suppresses stress-induced apoptosis in the granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent myeloid cell line MO7e and the lymphoblast HSC536 cells derived from a Fanconi anemia (FA) patient. " 07/01/1995 - "Two clinical trials were undertaken to evaluate the effect of human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) in pancytopenic pediatric patients with aplastic anemia and Fanconi's anemia. " 07/01/1995 - "GM-CSF clinical trials: pediatric aplastic anemia and Fanconi's anemia." 01/01/1994 - "Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of pancytopenia in children with fanconi anemia."
5.	Alkylating AgentsIBA 05/23/1979 - "Effects of alkylating agents on lymphocytes from controls and from patients with Fanconi's anemia. " 10/01/1975 - "Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi's anemia." 08/01/2010 - "Reduced doses of alkylating agents and radiotherapy are used in patients with Fanconi anemia. " 12/01/2007 - "Cells from Fanconi anemia (FA) patients are hypersensitive to alkylating agents and radiation traditionally used as conditioning regimens for marrow cell transplantation, and patients experience serious toxicities. " 11/01/2007 - "HSCT-1 was administered after myeloablative total body irradiation (TBI)- or alkylator-based conditioning for acute leukemias (N = 7), MDS (N = 6), CML (N = 2), and Fanconi anemia (N = 1). "
6.	Reactive Oxygen Species (Oxygen Radicals)IBA 08/15/2001 - "Several lines of evidence point to an abnormality in the response of Fanconi anemia cells to reactive oxygen species. " 07/14/2000 - "Fanconi's anemia (FA) is a clinically and genetically heterogeneous disease which has been hypothesized to be defective in the detoxification of reactive oxygen species. " 02/25/2000 - "Fanconi's anemia (FA) is a very rare genetically heterogeneous disease which has been hypothesized to be defective in the detoxification of reactive oxygen species. " 09/01/1992 - "The release of oxygen radicals by blood and bone marrow leukocytes of patients with Fanconi anemia (FA) has been studied. " 09/01/1992 - "Release of active oxygen radicals by leukocytes of Fanconi anemia patients."
7.	Proteins (Proteins, Gene)FDA Link 01/01/2015 - "The results of these studies suggest that the SLX4 complex is a conserved target of primate lentiviral Vpr proteins and that the ability to dysregulate members of the Fanconi anemia DNA repair pathway is essential for HIV/SIV replication in vivo." 01/01/2005 - "Recent studies show overlap between Fanconi anemia (FA) proteins and those involved in DNA repair mediated by homologous recombination (HR). " 12/15/2001 - "Studies have previously described the feasibility of receptor-mediated protein transfer in a cell culture model of Fanconi anemia (FA) group C. " 11/01/2023 - "The Fanconi anemia (FA) complex proteins AtFANCM, MHF1 and MHF2 were previously identified in a genetic screen as anti-CO factors that function during meiosis in Arabidopsis thaliana. " 09/28/2023 - "Here, we report that FANCD2-driven MiDAS in untransformed human cells: 1) requires a prerequisite step of FANCD2 mono-ubiquitination by a subset of Fanconi anemia (FA) proteins, 2) primarily acts to preserve CFS stability but not to prevent chromosome mis-segregation, and 3) depends on HELQ, which potentially functions at an early step. "
8.	diepoxybutaneIBA 03/01/2009 - "The objective of the present study was to determine the efficacy of this method for the diagnosis of 84 Brazilian patients with Fanconi anemia, all of whom tested positive for the diepoxybutane test, and 98 healthy controls. " 05/01/1983 - "Fanconi's anemia: a cytogenetic study on lymphocyte and bone marrow cultures utilizing 1,2:3,4-diepoxybutane." 03/01/2021 - "Surprisingly, as with the diepoxide 1,2:3,4-diepoxybutane (DEB), the monoepoxide EBD showed remarkable toxicity to cells deficient in Fanconi anemia (FANC) genes. " 01/01/2021 - "Of particular interest is a case presenting with a FANCL biallelic LoF variant and a positive diepoxybutane test but lacking a full Fanconi anemia phenotypic spectrum. " 01/01/2021 - "The diepoxybutane test was used to screen Fanconi Anemia. "
9.	Cisplatin (Platino)FDA LinkGeneric 10/04/2023 - "For this purpose, FaDu and UM-SCC1 cells were exposed to X-rays or cisplatin and treated with an ATR or Chk1 inhibitor, or by Fanconi anemia gene A knockout (FANCA ko). " 09/16/2022 - "And-1 Coordinates with the FANCM Complex to Regulate Fanconi Anemia Signaling and Cisplatin Resistance." 01/01/2017 - "The Fanconi anemia pathway in coordination with homologous recombination is essential to repair interstrand crosslinks (ICLs) caused by cisplatin. " 01/01/2017 - "Chronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways." 04/20/2016 - "Expression profiling revealed wide-spread transcriptional regulation of DNA repair genes and in particular Fanconi anemia (FA) pathway components such as FANCD2 and RAD18 - known to be crucial for the repair of cisplatin-induced interstrand crosslinks. "
10.	Mitomycin (Mitomycin-C)FDA LinkGeneric 09/01/1987 - "Studies of gene transfer and reversion to mitomycin C resistance in Fanconi anemia cells." 01/27/2023 - "Clinical and cytogenetic profile of Fanconi anemia diagnosed after implementation of mitomycin C cytogenetic test in the state of Pernambuco, Brazil." 01/09/2018 - "Reduced recruitment of 53BP1 during interstrand crosslink repair is associated with genetically inherited attenuation of mitomycin C sensitivity in a family with Fanconi anemia." 01/01/2018 - "In proof-of-principle experiments, we demonstrate application of the multiplex assay by quantifying the FANCD2 proteoforms following mitomycin-c treatment in an isogenic pair of FancA-corrected and uncorrected cell lines, as well as primary peripheral blood mononuclear cells from Fanconi Anemia patients. " 03/01/2016 - "Although both M1 and M2 polarized Fanconi anemia cells were predictably hypersensitive to mitomycin C, only M1 macrophages overproduced TNF-α in response to TLR-activating signals. "

Therapies and Procedures

1.	Cell Transplantation 01/01/2017 - "Hematopoietic cell transplantation for Fanconi Anemia (FA) has improved dramatically over the past 40 years. " 10/17/2023 - "Allogeneic hematopoietic cell transplantation (HCT) remains the only cure for the hematologic manifestations of Fanconi anemia (FA). " 10/31/2023 - "In Utero Hematopoietic Cell Transplantation Leads to Sustained Engraftment in a Mouse Model of Fanconi Anemia." 10/17/2023 - "Predictors of outcomes in hematopoietic cell transplantation for Fanconi anemia." 02/01/2022 - "Kidney complications in 107 Fanconi anemia patients submitted to hematopoietic cell transplantation."
2.	Hematopoietic Stem Cell Transplantation 01/01/2023 - "The aim of this study was to elaborate a specific protocol for the assessment and early identification of skin lesions in pediatric patients with Fanconi anemia undergoing hematopoietic stem cell transplantation. " 10/01/2017 - "This study aimed to characterize body composition of adult, children and adolescent patients with Fanconi anemia who were submitted to hematopoietic stem cell transplantation or not. " 10/25/2023 - "Hematopoietic stem cell transplantation in patients with Fanconi anemia: a report of late effects and psychosocial adjustment in life." 01/01/2023 - "Gonadal dysfunction and reduced fertility are clinical manifestations well described in patients with Fanconi anemia (FA) and following hematopoietic stem cell transplantation (HSCT). " 01/01/2023 - "The protocol developed gathers relevant and standardized information for the follow-up of patients with Fanconi anemia undergoing hematopoietic stem cell transplantation, ensuring greater reliability of the information, and its implementation will allow the prospective evaluation of patients."
3.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 03/01/2007 - "Bone marrow transplantation (BMT) is the only known cure for the hematologic manifestations of Fanconi anemia (FA). " 02/01/1995 - "Bone marrow transplantation for patients with Fanconi anemia: a study of 24 cases from a single institution." 01/01/2018 - "For the fatal genetic blood disorder Fanconi anemia, allogeneic bone marrow transplantation has remained the only curative treatment. " 10/01/2016 - "Preemptive Bone Marrow Transplantation and Event-Free Survival in Fanconi Anemia." 06/11/2015 - "In this issue of Blood, MacMillan et al give the results of sequential modifications of the conditioning regimen to improve the outcome of unrelated bone marrow transplantation in Fanconi anemia (FA). "
4.	Therapeutics 01/01/2020 - "While, unfortunately, none of the compounds tested were able to restore cellular FANCA-deficiency, our study shows the potential capacity to screen large compound libraries in the context of Fanconi anemia therapeutics in an optimized and cost-effective platform." 11/01/2018 - "This novel selection strategy has been approved by the regulatory agencies in a gene therapy study for Fanconi anemia patients (NCI Clinical Trial Reporting Program Registry ID NCI-2011-00202; clinicaltrials.gov identifier: 01331018)." 08/01/2015 - "Fanconi anemia: a model disease for studies on human genetics and advanced therapeutics." 01/01/2022 - "Inherited heterozygous Fanconi anemia gene mutations in a therapy-related CMML patient with a rare NUP98-HOXC11 fusion: A case report." 01/01/2020 - "High content drug screening for Fanconi anemia therapeutics."
5.	Drug Therapy (Chemotherapy) 12/01/2019 - "However, there are no published PK data in patients with Fanconi anemia (FA), who are known to have baseline DNA repair defect and related inherent sensitivity to chemotherapy. " 01/19/2017 - "Our work reveals the mechanistic basis for temporal and spatial control of FANCD2:FANCI monoubiquitination that is critical for chemotherapy responses and prevention of Fanconi anemia." 11/01/1996 - "MDR-AML includes most AML in the elderly, AML following MDS, AML complicating Fanconi's anemia, and a minor subset of AML in children; these subgroups appear to be linked by a common mutator phenotype, common genetic abnormalities, multilineage hematopoietic dysplasia, clonal hematopoiesis, and poor outcome with cytotoxic chemotherapy. " 08/01/2015 - "Outcomes of mismatched and unrelated donor hematopoietic stem cell transplantation in Fanconi anemia conditioned with chemotherapy only." 05/01/2015 - "The risk of developing MDS is relatively higher in some genetic syndromes such as Fanconi anemia and receipt of chemotherapy and radiation treatment. "