Severe telomere shortening in Fanconi anemia complementation group L.
Adolescent
Adult
Child
Child, Preschool
Chromosome Breakage
DNA-Binding Proteins
/ genetics
Fanconi Anemia
/ genetics
Fanconi Anemia Complementation Group A Protein
/ genetics
Fanconi Anemia Complementation Group G Protein
/ genetics
Fanconi Anemia Complementation Group L Protein
/ genetics
Female
Gene Expression Regulation
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Male
Telomere
/ genetics
Telomere Shortening
/ genetics
Young Adult
Chromosomal Instability
Fanconi anemia
Telomere Length
qPCR
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
06
10
2020
accepted:
16
12
2020
pubmed:
5
1
2021
medline:
21
5
2021
entrez:
4
1
2021
Statut:
ppublish
Résumé
Fanconi Anemia (FA) is a rare genetic disease with the incidence of 1 in 360,000 and is characterised by bone marrow failure, physical abnormalities, pancytopenia, and high frequency of chromosomal breakage and increased risk of evolving into malignancy. Telomere plays an important role in genomic stability, ageing process and cancers. Telomere shortening has been reported in FA. We studied telomere length in FA subjects and compared with complementation groups. Chromosomal breakage analysis from PHA stimulated, MMC induced peripheral blood culture was carried out in 37 clinically diagnosed FA. Molecular study of FANCA, G, and L was done through Sanger sequencing and next generation sequencing. Telomere length was estimated using real time quantitative polymerase chain reaction (qPCR) method. Student t-test was applied to test the significance. A high frequency of chromosomal breakage was observed in all the patients compared to healthy controls. We found significantly shorter telomere length in all the three complementation groups compare to age matched healthy controls. Among all complementation groups, FANCL showed severe telomere shortening (P value 0.0001). A negative correlation was observed between telomere length and chromosomal breakage frequency (R = -0.3116). Telomere shortening is not uncommon in FA subjects. However the telomere length shortening is different in complementation groups as FANCL showed severe telomere shortening in FA subjects. Though BM transplantation is essential for the management of the FA subjects, the telomere length can be considered as biological marker to understand the prognosis of the disease as FA subjects primarily treated with androgens.
Identifiants
pubmed: 33394227
doi: 10.1007/s11033-020-06101-2
pii: 10.1007/s11033-020-06101-2
doi:
Substances chimiques
DNA-Binding Proteins
0
FANCA protein, human
0
FANCG protein, human
0
Fanconi Anemia Complementation Group A Protein
0
Fanconi Anemia Complementation Group G Protein
0
FANCL protein, human
EC 2.3.2.27
Fanconi Anemia Complementation Group L Protein
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
585-593Subventions
Organisme : Department of Science and Technology, Government of India(IN)
ID : EEQ/2016/000510;B.R.V.
Références
Mehta PA, Tolar J (2002) Fanconi Anemia. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A (eds) GeneReviews. University of Washington, Seattle, pp 1993–2020
Hernández-Martínez A (2018) Fanconianemia. Med Interna Mex 34(5):730–734
Korgaonkar S, Ghosh K, Vundinti BR (2010) Clinical, genetic and cytogenetic study of Fanconianemia in an Indian population. Hematology 15(1):58–62
doi: 10.1179/102453310X12583347009531
Leteurtre F et al (1999) Accelerated telomere shortening and telomerase activation in Fanconi’s anaemia. Br J Haematology 105(4):883–893
doi: 10.1046/j.1365-2141.1999.01445.x
Joksic I et al (2012) Dysfunctional telomeres in primary cells from Fanconianemia FANCD2 patients. Genome Integr 3(1):1–12
doi: 10.1186/2041-9414-3-6
FA complementation groups HUGO Gene Nomenclature Committee. https://www.genenames.org/data/genegroup/#!/group/548. Accessed 22 Jun 2020
Shay JW (2018) Telomeres and aging. Curr Opin Cell Biol 52:1–7
doi: 10.1016/j.ceb.2017.12.001
Jose SS, Tidu F, Burilova P, Kepak T, Bendickova K, Fric J (2018) The telomerase complex directly controls hematopoietic stem cell differentiation and senescence in an induced pluripotent stem cell model of telomeropathy. Front Genet 9(2018):–345
Mehta S, Gulati S, Sharma N (2013) Aplastic Anemia, apoptosis and telomeres: insight into missing link and clinical implications. The association of physicians of India, Mumbai, pp 372–377
Kong CM, Lee XW, Wang X (2013) Telomere shortening in human diseases. FEBS J 280(14):3180–3193
doi: 10.1111/febs.12326
Hemann MT, Strong MA, Hao LY, Greider CW (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107(1):67–77
doi: 10.1016/S0092-8674(01)00504-9
Calado RT et al (2012) Short telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia. Leukemia 26(4):700–707
doi: 10.1038/leu.2011.272
Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB, Lansdorp PM (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci U S A 91(21):9857–9860
doi: 10.1073/pnas.91.21.9857
Li X et al (2003) Abnormal telomere metabolism in Fanconi’s anaemia correlates with genomic instability and the probability of developing severe aplastic anaemia. Br J Haematol 120(5):836–845
doi: 10.1046/j.1365-2141.2003.04225.x
Leteurtre F, Li X, Guardiola P et al (1999) Accelerated telomere shortening and telomerase activation in Fanconi’ s anaemia. 26: 883–893
Hanson H, Mathew CG, Docherty Z, Mackie Ogilvie C (2001) Telomere shortening in Fanconi anaemia demonstrated by a direct FISH approach. Cytogenet Cell Genet 93(3–4):203–206
doi: 10.1159/000056985
Filipović J et al (2016) First molecular-cytogenetic characterization of Fanconianemia fragile sites in primary lymphocytes of FA-D2 patients in different stages of the disease. Mol Cytogenet 9(1):1–10
doi: 10.1186/s13039-016-0280-6
Oostra AB, Nieuwint AWM, Joenje H, De Winter JP (2012) Diagnosis of Fanconi Anemia: chromosomal breakage analysis. Anemia 2012
Wysoczanska B et al (2019) Variability within the human TERT gene, telomere length and predisposition to chronic lymphocytic leukemia. Onco Targets Ther 12:4309–4320
doi: 10.2147/OTT.S198313
GraphPad Prism 7 Statistics Guide - Interpreting results: Correlation. https://www.graphpad.com/guides/prism/7/statistics/stat_interpreting_results_correlati.htm. Accessed 11 Sept 2020
Quick Statistics Calculators. https://www.socscistatistics.com/tests/. Accessed 11 Sept 2020
Martínez P, Blasco MA (2017) Telomere-driven diseases and telomere-targeting therapies. J Cell Biol 216(4):875–887
doi: 10.1083/jcb.201610111
Blasco MA (2008) Telomere binding proteins and disease. In: Rudolph KL (ed) Telomeres and telomerase in ageing, disease, and cancer. Springer-Verlag, Berlin, pp 229–244
doi: 10.1007/978-3-540-73709-4_12
Adelfalk C, Lorenz M, Serra V, Von Zglinicki T, Hirsch-Kauffmann M, Schweiger M (2001) Accelerated telomere shortening in Fanconianemia fibroblasts – a longitudinal study. FEBS Lett 506(1):22–26
doi: 10.1016/S0014-5793(01)02869-1
Alter BP, Giri N, Savage SA, Rosenberg PS (2015) Telomere length in inherited bone marrow failure syndromes. Haematologica 100(1):49–54
doi: 10.3324/haematol.2014.114389
Rhee DB, Wang Y, Mizesko M, Zhou F, Haneline L, Liu Y (2010) FANCC suppresses short telomere-initiated telomere sister chromatid exchange. Hum Mol Genet 19(5):879–887
doi: 10.1093/hmg/ddp556
Uziel O, Reshef H, Fabian I, Halperin D, Ram R, Bakhanashvili M (2008) Oxidative stress causes telomere damage in Fanconi anaemia cells – a possible predisposition for malignant transformation. Antioxid Redox Signal 10(11):1909–1921
doi: 10.1089/ars.2008.2129
Solanki A, Rajendran A, Mohan S, Raj R, Vundinti BR (2020) Mitochondrial DNA variations and mitochondrial dysfunction in Fanconianemia. PlosOne 15(1):1–11
doi: 10.1371/journal.pone.0227603
Young NS (2018) Aplastic anemia. N Engl J Med 379(17):1643–1656
doi: 10.1056/NEJMra1413485
Narita A et al (2015) Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia. Haematologica 100(12):1546–1552
doi: 10.3324/haematol.2015.132530
Scheckenbach K, Morgan M, Filger-Brillinger J, Sandmann M, Strimling B, Scheurlen W, Schindler D, Göbel U, Hanenberg H (2012) Treatment of the bone marrow failure in Fanconianemia patients with danazol. Blood Cells Mol Dis:128–131
Bagby GC, Lipton JM, Sloand EM, Schiffer CA (2004) Marrow failure. American Society of Hematology:318–336