Fanconi Anemia

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Ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, is implicated in the development and therapeutic responses of cancer. However, the role of ferroptosis-related gene profiles in lung squamous cell carcinoma (LSCC) remains largely unknown. The present study aimed to identify the prognostic roles of ferroptosis-related genes in LSCC. Sequencing data from the Cancer Genome Atlas were analyzed and ferroptosis-related gene expression between tumor and para-tumor tissue was identified...

BACKGROUND: Hematopoietic cell transplant (HCT) remains the only available curative treatment for Fanconi Anemia (FA), with particularly favorable outcomes reported after matched sibling donor (MSD) transplant. OBJECTIVES: To describe outcomes, with a special focus on late complications, in FA patients who underwent umbilical cord blood transplantation (UCBT). STUDY DESIGN: Retrospective analysis of allogeneic UCBT for FA performed between 1988 and 2021 in European Society for Blood and Marrow Transplantation (EBMT) affiliated centers...

The regulatory mechanism of gonadal sex differentiation, which is complex and regulated by multiple factors, remains poorly understood in teleosts. Recently, we have shown that compromised androgen and estrogen synthesis with increased progestin leads to all-male differentiation with proper testis development and spermatogenesis in cytochrome P450 17a1 (cyp17a1)-/- zebrafish. In the present study, the phenotypes of female-biased sex ratio were positively correlated with higher Fanconi anemia complementation group L (fancl) expression in the gonads of doublesex and mab-3 related transcription factor 1 (dmrt1)-/- and cyp17a1-/-;dmrt1-/- fish...

Fanconi anemia (FA) is an inherited DNA repair disorder characterized by bone marrow (BM) failure, developmental abnormalities, myelodysplasia, and leukemia and solid tumor predisposition. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a mainstay treatment, is limited by conditioning regimen-related toxicity and graft-versus-host disease (GVHD). Antibody-drug-conjugates (ADCs) targeting hematopoietic stem cells (HSCs) can open marrow niches permitting donor stem cell alloengraftment. Here, we report that single dose anti-mouse CD45-targeted-ADC (CD45-ADC) facilitated stable, multilineage chimerism in 3 distinct FA mouse models representing 90% of FA complementation groups...

Recent evidence has shed light on the significant role of FANCD2 in cancer initiation, development, and progression. However, a comprehensive pan-cancer analysis of FANCD2 has been lacking. In this study, we have conducted a thorough investigation into the expression profiles and prognostic significance of FANCD2, as well as its correlation with clinicopathological parameters and immune cell infiltration, using advanced bioinformatic techniques. The results demonstrate that FANCD2 is significantly upregulated in various common cancers and is associated with prognosis...

Demand-adjusted and cell type specific rates of protein synthesis represent an important safeguard for fate and function of long-term hematopoietic stem cells. Here, we identify increased protein synthesis rates in the fetal hematopoietic stem cell pool at the onset of hematopoietic failure in Fanconi Anemia, a prototypical DNA repair disorder that manifests with bone marrow failure. Mechanistically, the accumulation of misfolded proteins in Fancd2-/- fetal liver hematopoietic stem cells converges on endoplasmic reticulum stress, which in turn constrains midgestational expansion...

Colibactin is a secondary metabolite produced by bacteria present in the human gut and is implicated in the progression of colorectal cancer and inflammatory bowel disease. This genotoxin alkylates deoxyadenosines on opposite strands of host cell DNA to produce DNA interstrand cross-links (ICLs) that block DNA replication. While cells have evolved multiple mechanisms to resolve ("unhook") ICLs encountered by the replication machinery, little is known about which of these pathways promote resistance to colibactin-induced ICLs...

Fanconi anemia (FA) is the predominant hereditary syndrome of bone marrow failure (BMF), distinguished by impairments in DNA repair mechanisms. The deficiency in the FANC pathway, which governs DNA repair and replication rescue, results in aberrant responses to DNA damage in individuals with FA. The objective of this study is to examine the involvement of the FANC core complex in BMF and ascertain nucleolar homeostasis-related genes by conducting transcriptome analysis on primary hematopoietic stem cells obtained from FA patients with FANCA and FANCC variants...

OBJECTIVES: Neurocytomas (NCs) are rare intracranial tumors that can often be surgically resected. However, disease course is unpredictable in many patients and medical therapies are lacking. We have used whole exome sequencing to explore the molecular etiology for neurocytoma and assist in target identification to develop novel therapeutic interventions. METHODS: We used whole exome sequencing (WES) to compare the molecular landscape of 21 primary & recurrent NCs to five normal cerebellar control samples...

Patients with Fanconi anemia (FA) are often perceived to have poor growth when general population growth curves are utilized. We hypothesize that FA patients have unique growth and aimed to create FA-specific growth charts. Height and weight data from ages 0 to 20 years were extracted from medical records of patients treated at the Fanconi Anemia Comprehensive Care Clinic at the University of Minnesota. Height, weight, and BMI growth curves were generated and fitted to reference percentiles using the Lambda-Mu-Sigma method...

The purpose of the present study was to perform a systematic review focusing on oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) in Fanconi anemia (FA) individuals. Electronic searches were undertaken in five databases supplemented by manual scrutiny and gray literature. Case reports and/or cases series were included. The searches yielded 55 studies describing 112 cases of OSCC (n = 107) and/or OPMD (n = 5) in FA individuals. The mean age at diagnosis of OSCC/OPMD was 27...

In 2020, Fanconi anemia (FA) was classified as a syndrome with insufficient epidemiological evidence in the oral potentially malignant disorder (OPMD) group by the WHO Collaborating Centre. The paucity of case reports on FA-associated OPMD limits evidence-based management, and such cases have not been analyzed collectively in detail. Hence, the objective of this short communication is to summarize the evidence on the onset and progression of OPMD in FA patients, so as to better understand the natural history of oral cancer development in patients affected by FA...

Fanconi anemia (FA)-mutated acute myeloid leukemia (AML) is a secondary AML with very poor prognosis and limited therapeutic options due to increased sensitivity to DNA-damaging agents. PD-1 immune checkpoint inhibitors upregulate T-cell killing of cancer cells and is a class of promising treatment for FA-AML. Here, we developed a novel FA-AML murine model that allows the study of human AML with a humanized immune system in order to investigate immunotherapeutic treatments in vivo. FA-AML1 cells and non-FA-mutated Kasumi-1 cells were injected into 8-10 week old NSG mice...

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a serious liver disease worldwide, and its pathogenesis is complicated. AIMS: This study investigated the potential role of FANCA in the advancement and prognosis of LIHC. METHODS: Public databases, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot (WB) and immunohistochemistry (IHC) were employed to measure FANCA expression between tumor and normal samples...

INTRODUCTION: DNA double-strand breaks (DSBs) induced by ionizing radiation pose a significant threat to genome integrity, necessitating robust repair mechanisms. This study explores the responses of repair-deficient cells to low dose rate (LDR) radiation. Non-homologous end joining (NHEJ) and homologous recombination (HR) repair pathways play pivotal roles in maintaining genomic stability. The hypothesis posits distinct cellular outcomes under LDR exposure compared to acute radiation, impacting DNA repair mechanisms and cell survival...

The spectrum of childhood leukemia predisposition syndromes has grown significantly over last decades. These predisposition syndromes mainly involve CEBPA, ETV6, GATA2, IKZF1, PAX5, RUNX1, SAMD9/SAMD9L, TP53, RAS-MAPK pathway, DNA mismatch repair system genes, genes associated with Fanconi anemia, and trisomy 21. The clinico-biological features leading to the suspicion of a leukemia predisposition are highly heterogeneous and require varied exploration strategies. The study of the initial characteristics of childhood leukemias includes high-throughput sequencing techniques, which have increased the frequency of situations where a leukemia predisposing syndrome is suspected...

Accumulation of senescent cells in organs and tissues is a hallmark of aging and known to contribute to age-related diseases. Although aging-associated immune dysfunction, or immunosenescence, is known to contribute to this process, the underlying mechanism remains elusive. Here, we report that type 2 cytokine signaling deficiency accelerated aging and, conversely, that the interleukin-4 (IL-4)-STAT6 pathway protected macrophages from senescence. Mechanistically, activated STAT6 promoted the expression of genes involved in DNA repair both via homologous recombination and Fanconi anemia pathways...

BACKGROUND: Almost all patients with small cell lung cancer (SCLC) relapse. The therapeutic options of relapsed SCLC are limited, and the clinical outcomes are poor. Thus, genomic profiling of relapsed SCLC patients may help to develop more effective therapeutic options. METHODS: We collected blood specimens and follow-up information from a consecutive cohort of 31 patients diagnosed with relapsed SCLC in Zhongnan Hospital, Wuhan University, between 2018 and 2019, to analyze the comprehensive genomic profiling, and to investigate the impact of genomic alterations on therapeutic options and survival...

Pooled genetic screens are powerful tools to study gene function in a high-throughput manner. Typically, sequencing-based screens require cell lysis, which limits the examination of critical phenotypes such as cell morphology, protein subcellular localization, and cell-cell/tissue interactions. In contrast, emerging optical pooled screening methods enable the investigation of these spatial phenotypes in response to targeted CRISPR perturbations. In this study, we report a multi-omic optical pooled CRISPR screening method, which we have named CRISPRmap...