Bone Marrow Failure in Fanconi Anemia: Clinical and Genetic Spectrum in a Cohort of 20 Pediatric Patients

Kelaïdi, Charikleia; Makis, Alexandros; Petrikkos, Loizos; Antoniadi, Kondilia; Selenti, Nikoletta; Tzotzola, Vasiliki; Ioannidou, E.; Tsitsikas, Konstantinos; Kitra, Vasiliki; Kalpini-Mavrou, Ariadni; Fryssira, Helen; Polychronopoulou, Sophia

doi:10.1097/mph.0000000000001549

Cited by 12 publications

(6 citation statements)

References 32 publications

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“…The use of EWOG's histological criteria 2 and molecular findings such as SAMD9/SAMD9L mutations 28 may be useful for precise diagnosis and accurate prognosis. Recognising inherited conditions predisposing to SAA, better response prediction to IST, and optimal use of upfront HCT, may render possible further outcome improvement 29,30 …”

Section: Discussionmentioning

confidence: 99%

Severe aplastic anaemia in children: Impact of histopathology profile and treatment on very long‐term outcomes

et al. 2020

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Aim To assess very long‐term outcomes of children with severe aplastic anaemia (SAA) and impact of histopathology and of different treatments over time. Methods We conducted a retrospective study of 57 consecutive patients with SAA during 1973‐2019. According to period, treatment consisted of androgens, immunosuppressive treatment (IST) and haematopoietic cell transplantation (HCT) in 14, 31 and 13 patients, respectively. Histopathology immune profiles were studied on bone marrow (BM). Results Response rate (RR) to androgens was 35%, with long‐term survivorship in 4 of 5 responders. RR and 10‐year overall survival (OS) after IST was 65% and 80%, respectively. RR was higher in girls (92% vs 43% in boys, P = .02). Mean baseline BM values of CD34 + and of B‐lymphocytes in responders vs non‐responders were 1.3% vs 0 (P = .08) and 14.1% vs 9.7% (P = .07), respectively. After IST, BM cellularity gradually increased and cytotoxic T‐lymphocytes decreased (time variation P = .003 and 0.07, respectively). Outcome did not differ between patients with IST or frontline HCT. Ten‐year OS improved over time, increasing from 35.3% to 77.1% and 77% during 1973‐1985, 1986‐2003 and 2004‐2019, respectively. Conclusion Histopathology may refine response prediction to IST. The course of SAA in children, a previously fatal disease, was altered in recent times.

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Section: Discussionmentioning

confidence: 99%

Severe aplastic anaemia in children: Impact of histopathology profile and treatment on very long‐term outcomes

et al. 2020

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“…Fanconi anemia (FA) is a rare recessive disorder characterized by anemia and bone marrow failure. It is caused by mutations in the FA family proteins ( 7 , 8 ). The FA family consists of ~19 genes associated with cell cycle progression, regulation and DNA damage repair ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

UBE2T regulates FANCI monoubiquitination to promote NSCLC progression by activating EMT

Zhang

Wang

et al. 2022

Oncol Rep

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Fanconi anemia complementation group I (FANCI) is a critical protein for maintaining DNA stability. However, the exact role of FANCI in tumors remains to be elucidated. The present study aimed to explore the role and potential mechanism of action of FANCI in non-small cell lung cancer (NSCLC). To quantify the expression levels of FANCI and ubiquitin-conjugating enzyme E2T (UBE2T) in NSCLC tissues, reverse-transcription quantitative PCR and western blotting were employed. Cell Counting Kit-8, wound healing and Transwell assays along with flow cytometry analysis and tumor xenograft were used to investigate the biological effects of FANCI in NSCLC in vitro and in vivo . The binding of FANCI with UBE2T was confirmed using a co-immunoprecipitation assay. Epithelial-to-mesenchymal transition (EMT) protein markers were quantified via western blotting. The results showed that FANCI expression level was higher in NSCLC tumor tissues, compared with adjacent tissues. In A549 and H1299 cells, knockdown of FANCI inhibited cell proliferation, migration, invasion, cell cycle and EMT in vitro . Tumor growth was repressed in vitro , upon downregulation of FANCI expression. UBE2T was observed to directly bind to FANCI and regulate its monoubiquitination. Overexpression of UBE2T reversed the effects induced by FANCI knockdown in NSCLC cells. Furthermore, it was noted that FANCI interacted with WD repeat domain 48 (WDR48). Overexpression of WDR48 reversed the effects of FANCI on cell proliferation, migration and EMT. In conclusion, FANCI was identified to be a putative oncogene in NSCLC, wherein FANCI was monouniubiquitinated by UBE2T to regulate cell growth, migration and EMT through WDR48. The findings suggested that FANCI could be used as a prognostic biomarker and therapeutic target for NSCLC.

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“…Fanconi anemia (FA) is caused by the mutation of the FA family protein, and can lead to chromosome instability and other diseases, including cancer (21,22 (25).…”

Section: Discussionmentioning

confidence: 99%

miRNA-218/FANCI is associated with metastasis and poor prognosis in lung adenocarcinoma: a bioinformatics analysis

Ye¹,

Liu²,

Huang³

et al. 2021

Ann Transl Med

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Background: In this study, tumor microarray analysis was used to screen the key messenger RNAs (mRNAs) and microRNAs related to the progression of lung adenocarcinoma (LUAD), in order to provide a theoretical basis for early diagnosis, therapeutic targets, and prognosis evaluation of patients with LUAD. Methods:The mRNA and miRNA expression datasets came from the Gene Expression Omnibus (GEO) project database. Differentially expressed genes (DEGs) and microRNAs (DEMs) between LUAD tissues and adjacent lung tissue were obtained using GEO2R. The Search Tool for the Retrieval of Interacting Genes website was also employed to construct and visualize the interactions of overlapped DEGs. The overall survival of DEMs was investigated using the Kaplan-Meier plotter. The TargetScan website (http://www.targetscan.org/) was used to verify the relationship between FA Complementation Group I (FANCI) and the expression of miRNA-218 (miR-218). The expression of FANCI was verified using the GEO and Human Protein Atlas databases, as well as Real Time Quantitative PCR using our own samples. Next, we analyzed the relationship between the expression of FANCI and the clinicopathological characteristics as well as the prognosis of patients with LUAD. We also explored whether the FANCI was related to immune cell infiltration in LUAD.Results: FANCI was identified as a hub gene and associated with poor OS. We found that miR-218 negatively regulates FANCI mRNA expression. At the mRNA expression and protein level, FANCI was more highly expressed in LUAD tissues. The expression of FANCI in LUAD was related to tumor size (χ 2 =13.96, P<0.001), lymphatic metastasis (χ 2 =3.88, P<0.05), distant metastasis (χ 2 =45.39, P<0.001), and stage (χ 2 =11.03, P<0.05). In addition, the Cox regression model found that FANCI mRNA expression was an independent predictive factor of patient survival (P<0.05). FANCI expression was both weakly related to B cells and neutrophil infiltration in LUAD.Conclusions: miR-218 may negatively regulate FANCI, and FANCI could promote metastasis via extracellular matrix (ECM) receptor interaction, leading to poor prognosis of LUAD. FANCI may be a key gene to the determine metastasis and poor prognosis in patients with LUAD. Changes in the immune microenvironment may be the mechanism through which FANCI leads to poor prognosis of LUAD.

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Bone Marrow Failure in Fanconi Anemia: Clinical and Genetic Spectrum in a Cohort of 20 Pediatric Patients

Cited by 12 publications

References 32 publications

Severe aplastic anaemia in children: Impact of histopathology profile and treatment on very long‐term outcomes

Severe aplastic anaemia in children: Impact of histopathology profile and treatment on very long‐term outcomes

UBE2T regulates FANCI monoubiquitination to promote NSCLC progression by activating EMT

miRNA-218/FANCI is associated with metastasis and poor prognosis in lung adenocarcinoma: a bioinformatics analysis

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