KLF transcription factor 1 (KLF1) and GATA binding protein 1 (GATA1) are transcription factors (TFs) that initiate and regulate transcription of the genes involved in erythropoiesis. These TFs possess DNA-binding domains that recognize specific nucleotide sequences in genes, to which they bind and regulate transcription. Variants in the genes that encode either KLF1 or GATA1 can result in a range of hematologic phenotypes-from benign to severe forms of thrombocytopenia and anemia; they can also weaken the expression of blood group antigens. The Lutheran (LU) blood group system is susceptible to TF gene variations, particularly KLF1 variants. Individuals heterozygous for KLF1 gene variants show reduced Lutheran antigens on red blood cells that are not usually detected by routine hemagglutination methods. This reduced antigen expression is referred to as the In(Lu) phenotype. For accurate blood typing, it is important to distinguish between the In(Lu) phenotype, which has very weak antigen expression, and the true Lunull phenotype, which has no antigen expression. The International Society of Blood Transfusion blood group allele database registers KLF1 and GATA1 variants associated with modified Lutheran expression. Here, we review KLF1 and recent novel gene variants defined through investigating blood group phenotype and genotype discrepancies or, for one report, investigating cases with unexplained chronic anemia. In addition, we include a review of the GATA1 TF, including a case report describing the second GATA1 variant associated with a serologic Lu(a-b-) phenotype. Finally, we review both past and recent reports on variations in the DNA sequence motifs on the blood group genes that disrupt the binding of the GATA1 TF and either remove or reduce erythroid antigen expression. This review highlights the diversity and complexity of the transcription process itself and the need to consider these factors as an added component for accurate blood group phenotyping.

Long noncoding RNAs (lncRNAs), as gene expression modulators, are potential players in Acute Lymphoblastic Leukemia (ALL) pathogenesis. We systematically explored current literature on lncRNA expression in ALL to identify lncRNAs consistently reported as differentially expressed (DE) either in ALL versus controls or between ALL subtypes. By comparing articles that provided global expression data for DE lncRNAs in the ETV6::RUNX1-positive ALL subtype, we identified four DE lncRNAs in three independent studies (two versus other subtypes and one versus controls), showing concordant expression of LINC01013, CRNDE and lnc-KLF7-1. Additionally, LINC01503 was consistently downregulated on ALL versus controls. Within RT-qPCR studies, twelve lncRNA were DE in more than one source. Thus, several lncRNAs were supported as DE in ALL by multiple sources, highlighting their potential role as candidate biomarkers or therapeutic targets. Finally, as lncRNA annotation is rapidly expanding, standardization of reporting and nomenclature is urgently needed to improve data verifiability and compilation.

Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is found in different human tissues and shows diverse regulatory activities in a cell-dependent manner. In the brain, KLF4 controls various neurophysiological and neuropathological processes, and its contribution to various neurological diseases has been widely reported. Parkinson\'s disease (PD) is an age-related neurodegenerative disease that might have a connection with KLF4. In this review, we discussed the potential implication of KLF4 in fundamental molecular mechanisms of PD, including aberrant proteostasis, neuroinflammation, apoptosis, oxidative stress, and iron overload. The evidence collected herein sheds new light on KLF4-mediated pathways, which manipulation appears to be a promising therapeutic target for PD management. However, there is a gap in the knowledge on this topic, and extended research is required to understand the translational value of the KLF4-oriented therapeutical approach in PD.

We present the clinicopathological and molecular genetic characteristics of a neuroepithelial tumor (NET), EWSR1::PATZ1 fusion-positive with a literature review. This fusion has recently been discovered in rare central nervous system tumors and soft tissue sarcomas and was not included in the fifth edition of the WHO classifications. We identified this fusion in 2 NETs. The first case involved a 7-year-old girl and the second case occurred in a 53-year-old man; both presented with headaches and vomiting. The pediatric case initially showed an intermediate grade of the tumor, but upon recurrences, it transformed into a high-grade tumor with 2 relapses in 8.3 years. This case exhibited high mitotic activity (20/10 high-power fields), and a high Ki-67 index (21%). The TERT promoter (TERTp) mutation was present in both initial and recurrent tumors. In contrast, the adult case was a low-grade tumor with no mitotic activity or recurrence over 13.5 months after subtotal resection and gamma knife surgery. Interestingly, the pediatric case demonstrated a longer survival time compared to conventional glioblastoma. The TERTp mutation, similar to being a molecular signature in adult-type glioblastoma, could also be an indicator of high-grade behavior in PATZ1 fusion NET.

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UNASSIGNED: This systematic review and meta-analysis focussed on insights into the relationship between CACNA1C-rs1006737 and ZNF804A-rs1344706 polymorphisms and cognitive performance in schizophrenia (SCZ) spectrum and bipolar disorder (BD) and provide some contributions for clinical practice.
UNASSIGNED: We searched the websites databases (PubMED, PsycINFO, Web of Science, EMBASE and Cochrane Library) using eligibility and exclusion criteria to capture all potential studies, based on PICO model and according to the PRISMA.
UNASSIGNED: Eight articles were included in this systematic review (five referring to CACNA1C-rs1006737 and three related to ZNF804A-rs1344706 polymorphisms), with a total of 5759 participants (1751 SCZ patients, 348 BD patients, 3626 controls and 34 first-degree relatives). The results demonstrated that the pooled effect of CACNA1C-rs1006737 (risk difference RD = 0.08; 95% CI 0.02-0.15) was associated with altered cognitive function in patients with severe mental disorders, but not ZNF804A-rs1344706 polymorphism (RD = 0.19; 95% CI 0.09-0.48.
UNASSIGNED: The present meta-analysis provides evidence regarding slight association between CACNA1C-rs1006737 polymorphisms and cognitive performance in severe mental disorders, indicating that cognitive impairment in severe mental disorders associated with the CACNA1C rs1006737 risk variants could only be expressed when interacting with environmental exposures. This study is registered with PROSPERO, number CRD42021246726.

Previous studies and meta-analysis indicated that rs1344706 was associated with schizophrenia in European population, whereas the conclusions in other populations were disputed. To further explore whether the allele A of rs1344706 would increase the risk of schizophrenia in different populations and update the original meta-analysis, we conducted a systematic review and meta-analysis worldwide.
A literature search was performed in PubMed, Embase, Cochrane Library, PsycINFO and Web of Science (up to 10 July 2019) according to the inclusion criteria.
A total of 27 articles were included. Our meta-analysis showed an association between rs1344706 and schizophrenia in total populations [P = 0.000; odds ratio (OR) = 1.105; 95% confidence interval (CI), 1.048-1.165], Europe population (P = 0.025; OR = 1.108; 95% CI, 1.013-1.222) and Asian population(P = 0.005; OR = 1.094; 95% CI, 1.027-1.164).
Our findings suggested that the risk of single nucleotide polymorphism rs1344706 A-allele may increase the risk of schizophrenia worldwide. Also, this ethnicity-dependent effects of ZNF804A variant on schizophrenia may be related to the opposite allele direction. But to elucidate the underlying biological mechanism, further studies with large participant populations are needed.

Sarcoma with EWSR1-PATZ1 gene fusion is an exceedingly rare and newly described Ewing-like sarcoma harboring EWSR1 rearrangements involving fusion partners other than ETS family genes. The clinical, histopathologic and immunophenotypic features of cases reported in literature are fairly diverse and not specific. We report a new case report posing real challenges for histological and molecular diagnosis.

EWSR1-PATZ1 is a rare gene fusion recently recognized to occur in round and spindle cell sarcomas. To date, fewer than 20 cases have been described in the literature. However, no dedicated case reports have detailed its presentation in the head and neck region. We recently cared for a 52-year-old woman with an isolated, single right level 5A cervical mass. Excisional biopsy at an external hospital revealed pathology results consistent with EWSR1-PATZ1 polyphenotypic round and spindle cell sarcoma. The patient subsequently underwent surgical excision of the tumor and right neck lymph node dissection followed by adjuvant chemoradiation. Laryngoscope, 2020.

Endometrial cancer is one of the most commonly diagnosed cancers in women. Although there is a hereditary component to endometrial cancer, most cases are thought to be sporadic and lifestyle related. The aim of this study was to systematically review prospective and retrospective case-control studies, meta-analyses and genome-wide association studies to identify genomic variants that may be associated with endometrial cancer risk.
We searched MEDLINE, Embase and CINAHL from 2007 to 2019 without restrictions. We followed PRISMA 2009 guidelines. The search yielded 3015 hits in total. Following duplicate exclusion, 2674 abstracts were screened and 453 full-texts evaluated based on our pre-defined screening criteria. 149 articles were eligible for inclusion.
We found that single nucleotide polymorphisms (SNPs) in HNF1B, KLF, EIF2AK, CYP19A1, SOX4 and MYC were strongly associated with incident endometrial cancer. Nineteen variants were reported with genome-wide significance and a further five with suggestive significance. No convincing evidence was found for the widely studied MDM2 variant rs2279744. Publication bias and false discovery rates were noted throughout the literature.
Endometrial cancer risk may be influenced by SNPs in genes involved in cell survival, oestrogen metabolism and transcriptional control. Larger cohorts are needed to identify more variants with genome-wide significance.