A retrospective analysis was conducted on a MonoMAC syndrome case admitted in October 2022 to the First Affiliated Hospital of Zhejiang University School of Medicine. The patient, a 16-year-old female with a history of persistent monocytopenia and mild anemia for several years, experienced recurrent symptoms of cough, expectoration, and fever, leading to multiple visits to the hospital. The diagnosis of MonoMAC syndrome was confirmed through comprehensive assessments including routine blood tests, pathogen metagenomic sequencing, lung and bone marrow biopsies, and next-generation sequencing of peripheral blood. The patient underwent haploidentical hematopoietic stem cell transplantation, with a smooth course of transplantation, achieving neutrophil engraftment on + 16 d and platelet engraftment on + 17 d, eventually restoring normal monocyte and NK cell counts. MonoMAC syndrome patients often initially present with infectious symptoms, and the diagnosis can be established based on significant monocytopenia in routine blood tests, history of non-tuberculous mycobacterial infections, and GATA2 germline mutations. Allogeneic hematopoietic stem cell transplantation may be required for some patients to improve their prognosis.
回顾性分析浙江大学医学院附属第一医院2022年10月收治的1例MonoMAC综合征病例，女性，16岁，有多年外周血单核细胞数减少及轻度贫血病史，因\"反复咳嗽咯痰伴发热\"在浙江大学医学院附属第一医院多次就诊，最终结合血常规、病原学宏基因组测序、肺穿刺活检、骨髓穿刺活检及外周血二代测序等检查，诊断为MonoMAC综合征，并接受单倍体造血干细胞移植。患者移植过程较顺利，+16 d粒细胞植入，+17 d血小板植入，最终单核细胞数和NK细胞数恢复正常。MonoMAC综合征患者常因感染症状首次就诊，结合血常规中单核细胞明显减低，非结核分枝杆菌感染史、GATA2胚系突变等检查结果可确诊。部分患者需行异基因造血干细胞移植治疗以改善预后。.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is a syndrome that occurs in patients with severe systemic hyperinflammation. GATA binding protein 2 (GATA2) is a transcription factor and key component in haematopoiesis and stem cell biology.
METHODS: Three patients with HLH, one with Mycobacterium avium infection, one with Epstein-Barr virus (EBV) infection, and one with Mycobacterium kansasii infection, were all subsequently found to have a defect in the GATA2 gene through genetic testing.
CONCLUSIONS: GATA2 deficiency syndrome should be considered in patients with myelodysplastic syndrome, nontuberculous mycobacterium infection and HLH. In addition, the GATA2 gene variant may be a genetic defect that could be the cause of the primary HLH. However, further studies are needed to confirm the role of GATA2 pathogenic variants in the pathogenesis of HLH.

During hematopoiesis, megakaryocytic erythroid progenitors (MEPs) differentiate into megakaryocytic or erythroid lineages in response to specific transcriptional factors, yet the regulatory mechanism remains to be elucidated. Using the MEP‑like cell line HEL western blotting, RT‑qPCR, lentivirus‑mediated downregulation, flow cytometry as well as chromatin immunoprecipitation (ChIp) assay demonstrated that the E26 transformation‑specific (ETS) transcription factor friend leukemia integration factor 1 (Fli‑1) inhibits erythroid differentiation. The present study using these methods showed that while FLI1‑mediated downregulation of GATA binding protein 1 (GATA1) suppresses erythropoiesis, its direct transcriptional induction of GATA2 promotes megakaryocytic differentiation. GATA1 is also involved in megakaryocytic differentiation through regulation of GATA2. By contrast to FLI1, the ETS member erythroblast transformation‑specific‑related gene (ERG) negatively controls GATA2 and its overexpression through exogenous transfection blocks megakaryocytic differentiation. In addition, FLI1 regulates expression of LIM Domain Binding 1 (LDB1) during erythroid and megakaryocytic commitment, whereas shRNA‑mediated depletion of LDB1 downregulates FLI1 and GATA2 but increases GATA1 expression. In agreement, LDB1 ablation using shRNA lentivirus expression blocks megakaryocytic differentiation and modestly suppresses erythroid maturation. These results suggested that a certain threshold level of LDB1 expression enables FLI1 to block erythroid differentiation. Overall, FLI1 controlled the commitment of MEP to either erythroid or megakaryocytic lineage through an intricate regulation of GATA1/GATA2, LDB1 and ERG, exposing multiple targets for cell fate commitment and therapeutic intervention.

OBJECTIVE: To analyze the occurrence of concomitant gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients with CEBPA mutation and its impact on the clinical characteristics and prognosis of the patients.
METHODS: 151 newly diagnosed patients with CN-AML in the Second Hospital of Shanxi Medical University from June 2013 to June 2020 were analyzed retrospectively. 34 common genetic mutations associated with hematologic malignancies were detected by next-generation sequencing technology. The occurrence of concomitant gene mutations in patients with CEBPA positive and negative groups was compared, and the correlation between concomitant mutations in different functional groups and the clinical characteristics and prognosis of CN-AML patients with CEBPA mutation was analyzed.
RESULTS: In 151 patients with CN-AML, 55 (36.42%) were positive for CEBPA mutation (including 36 cases of CEBPAdm and 19 cases of CEBPAsm), of which 41 (74.55%) had co-mutations with other genes. The main mutated genes were GATA2 (25.45%, 14/55), TET2 (21.82%, 12/55), FLT3 (20.00%, 11/55), NRAS (12.73%, 7/55) and WT1 (9.09%, 9/55), etc. Some cases had two or more concomitant gene mutations. Grouping the mutant genes according to their functions showed that CEBPA+ group had lower mutation rates of histone methylation (P =0.002) and chromatin modification genes (P =0.002, P =0.033), and higher mutation rates of transcription factors (P =0.037) than CEBPA- group. In 55 patients with CEBPA+ CN-AML, the platelet count at diagnosis in signaling pathway gene mutation-positive group was lower than that in the mutation-negative group (P =0.005), the proportion of bone marrow blasts in transcription factor mutation-positive group was higher than that in the mutation-negative group (P =0.003), and the onset age in DNA methylation gene mutation-positive group and chromatin modifier mutation-positive group was older than that in the mutation-negative group, respectively (P =0.002, P =0.008). DFS of CEBPA+ CN-AML patients in signaling pathway gene mutation group was shorter than that in signaling pathway gene mutation-negative group (median DFS: 12 months vs not reached) (P =0.034). Compared with DNA methylation gene mutation-negative group, CEBPA+ CN-AML patients with DNA methylation gene mutation had lower CR rate (P =0.025) significantly shorter OS and DFS (median OS: 20 months vs not reached, P =0.006; median DFS: 15 months vs not reached, P =0.049). OS in patients with histone methylation gene mutation was significantly shorter than that in the histone methylation gene mutation-negative group (median OS: 12 months vs 40 months) (P =0.008). Multivariate analysis of prognostic factors showed that the proportion of bone marrow blasts (P =0.046), concomitant DNA methylation gene mutation (P =0.006) and histone methylation gene mutation (P =0.036) were independent risk factors affecting the prognosis.
CONCLUSIONS: CN-AML patients with CEBPA mutation have specific concomitant gene profile, and the concomitant mutations of different functional genes have a certain impact on the clinical characteristics and prognosis of the patients.
UNASSIGNED: CEBPA突变CN-AML伴不同功能基因突变患者的临床特征及预后分析.
UNASSIGNED: 分析CEBPA突变正常核型急性髓系白血病（CN-AML）患者伴随基因突变发生的情况，及其对患者临床特征及预后的影响。.
UNASSIGNED: 回顾性分析2013年6月至2020年6月就诊于山西医科大学第二医院的151例初诊CN-AML患者，通过第二代DNA测序技术检测34种常见血液肿瘤基因突变情况；比较CEBPA+与CEBPA-患者的伴随基因突变发生情况，分析不同功能的基因突变与CEBPA+ CN-AML患者临床特征及预后的相关性。.
UNASSIGNED: 在151例CN-AML患者中共检测到55例（36.42%）CEBPA+突变（包括36例CEBPA双突变，19例CEBPA单突变），其中41例（74.55%）与其他基因存在共突变，主要突变基因为：GATA2 14 例（25.45%）、 TET2 12 例（21.82%）、FLT3 11例 （20.00%）、 NRAS 7例（12.73%）和WT1 5例（9.09%），部分病例同时存在2种及2种以上伴随基因突变。将突变基因按照功能进行分组后发现，CEBPA+组较CEBPA-组具有更低的组蛋白甲基化及染色质修饰基因伴随突变率（P = 0.002，P =0.033）、更高的转录因子基因伴随突变率（P =0.037）。55例CEBPA+CN-AML患者中，伴信号通路基因突变阳性组患者初诊时血小板计数低于突变阴性组（P =0.005），伴转录因子基因突变阳性组的骨髓原始细胞比例高于突变阴性组（P =0.003），伴DNA甲基化基因和染色质修饰基因突变阳性组的发病年龄均明显大于相应突变阴性组（P =0.002，P =0.008）。伴随信号通路基因突变阳性组CEBPA+ CN-AML患者的DFS短于阴性组（12个月vs 未达到）（P =0.034）。伴DNA甲基化基因突变阳性组较阴性组患者具有更低的CR率（P =0.025），且OS和DFS均显著短于阴性组（中位OS：20个月vs 未达到，P =0.006；中位DFS：15个月vs 未达到，P =0.049）。伴组蛋白甲基化基因突变阳性组患者的OS显著短于阴性组（中位OS：12个月vs 40个月）（P =0.008）。多因素分析显示，骨髓原始细胞比例（HR =4.306）、伴DNA甲基化基因突变（HR =9.917）及组蛋白甲基化基因突变（HR =5.764）是影响CN-AML患者预后的独立危险因素。.
UNASSIGNED: CEBPA+CN-AML患者有其特定的伴随基因表达谱，且伴随不同功能基因突变对患者的临床特征及预后有一定影响。.

OBJECTIVE: To investigate the clinical characteristics, coexisting gene mutations and prognosis of acute myeloid leukemia (AML) patients with GATA2 gene mutation.
METHODS: The clinical data of 370 newly diagnosed AML patients treated in our hospital from January 2008 to January 2021 was analyzed retrospectively, the next-generation sequencing technology was used to detect the mutated genes in those patients. The clinical characteristics of AML patients with GATA2 mutations, the co-mutated genes of GATA2 mutations, and the effect of GATA2 mutation on prognosis were analyzed.
RESULTS: A total of 23 patients (6.2%) with GATA2 mutation was detected in 370 AML patients. Compared with GATA2 non-mutation group, patients in GATA2 mutation group were mostly normal karyotypes (P =0.037) and in low-risk cytogenetic stratification (P =0.028). The incidence of CEBPAdm and NRAS in GATA2 mutation group was significantly higher than that in GATA2 non-mutation group (P =0.010, P =0.009). There were no statistically significant differences between the two groups in terms of sex, age, white blood cell count (WBC), platelet count, hemoglobin, bone marrow (BM) blast, induction chemotherapy regimen and CR rate (P >0.05). Among the 23 patients with GATA2 mutation, the most common co-mutated genes were CEBPAdm, NRAS (both 39.1%), NPM1, FLT3, TET2, WT1 (all 17.4%), ASXL1 and IDH1 (both 13.0%). Survival analysis showed that there was no statistical difference in 5-year overall survival (OS) and leukemia-free survival (LFS) rates between patients with and without GATA2 mutations in whole cohort (n=370) (P =0.306, P =0.308). Among 306 patients without CEBPAdm, the 5-year OS and LFS rates in GATA2 mutation group showed an increasing trend compared with GATA2 non-mutation group, but the difference was not statistically significant (P =0.092, P =0.056). Among 64 patients with CEBPAdm, there was no statistically significant difference in 5-year OS rate between the GATA2 mutation group and the GATA2 non-mutation group (P =0.104), but the 5-year LFS rate of the GATA2 mutation group was significantly decreased (P =0.047). Among the 23 patients with GATA2 mutation, 16 cases received the \"3+7\" induction regimen, of which 12 cases received allogeneic hematopoietic stem cell transplantation (allo-HSCT); 7 cases received the \"DCAG\" induction regimen, of which 3 cases received allo-HSCT. The CR rate was not statistically different between the \"3+7\" regimen group and the \"DCAG\" regimen group (P =1.000). The 5-year OS rate and LFS rate in the transplantation group were significantly higher than the chemotherapy group (P =0.021, P =0.020).
CONCLUSIONS: GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification, and it is significantly associated with CEBPAdm and NRAS co-mutations. The prognostic significance of GATA2 is influenced by CEBPAdm. The choice of \"3+7\" or \"DCAG\" induction regimen in patients with GATA2 mutation does not affect their CR rate, while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.
UNASSIGNED: 伴GATA2基因突变的急性髓系白血病患者的临床特征及预后分析.
UNASSIGNED: 探讨伴有GATA2基因突变的急性髓系白血病（AML）患者的临床特征、共存突变基因及其对预后的 影响。.
UNASSIGNED: 回顾性分析2008年1月至2021年1月就诊于解放军总医院第一医学中心血液科的370例初诊AML患者的临床资料，应用二代基因测序技术检测其突变基因，分析AML中GATA2突变患者的临床特征、GATA2突变的共变基因及GATA2突变对预后的影响。.
UNASSIGNED: 370例AML患者中，共23例（6.2%）患者检测到GATA2突变。与GATA2未突变组相比，GATA2突变组患者多属于正常核型（P =0.037）且多处于低危细胞遗传学分层（P =0.028）， CEBPAdm、NRAS 在GATA2突变组的发生率显著高于GATA2未突变组（P =0.010，P =0.009），两组在性别、年龄、白细胞数、血小板数、血红蛋白、原始细胞数、诱导方案、CR率方面的差异均无统计学意义（P >0.05）。23例伴有GATA2突变的患者中主要共存基因突变依次为 CEBPAdm、NRAS （均为39.1%），NPM1、FLT3、TET2、WT1（均为17.4%），ASXL1、IDH1（均为13.0%）。生存分析结果显示，在整个队列中，伴GATA2突变组患者与不伴GATA2突变组患者5年总生存（OS）及无白血病生存（LFS）率无统计学差异（P =0.306，P =0.308）；在306例不伴 CEBPAdm的患者中，GATA2突变组患者较GATA2未突变组患者5年OS率及LFS率均有提高趋势，但差异未达统计学意义（P =0.092，P =0.056）；而在64例伴 CEBPAdm的患者中，GATA2突变组患者与GATA2未突变组患者5年OS率无统计学差异（P =0.104），但GATA2突变组患者5年LFS率显著降低（P =0.047）。23例GATA2突变患者中，16例接受“3+7”诱导方案，其中12例接受异基因造血干细胞移植；7例接受“DCAG”诱导方案，其中3例接受移植。“3+7”方案组与“DCAG”方案组相比，CR率无统计学差异（P =1.000）。移植组较化疗组5年OS率及LFS率显著提高（P =0.021，P =0.020）。.
UNASSIGNED: GATA2突变显著多见于核型正常及低危细胞遗传学分层的AML患者，与 CEBPAdm、NRAS 共突变显著相关。GATA2对预后的意义受 CEBPAdm共突变影响。GATA2突变患者诱导方案选择“3+7”方案或“DCAG”方案不影响其CR率，而选择异基因造血干细胞移植相较于化疗能显著改善预后.

Drug resistance in breast cancer (BC) is a clinical challenge. Exploring the mechanism and identifying a precise predictive biomarker for the drug resistance in BC is critical. Three first-line drug (paclitaxel, doxorubicin and tamoxifen) resistance datasets in BC from GEO were merged to obtain 1,461 differentially expressed genes for weighted correlation network analysis, resulting in identifying ATRX as the hub gene. ATRX is a chromatin remodelling protein, therefore, ATRX-associated transcription factors were explored, thereby identifying the network of AR, GLI3 and GATA2. GO and KEGG analyses revealed immunity, transcriptional regulation and endocrinotherapy/chemotherapy resistance were enriched. Moreover, CIBERSORT revealed immunity regulation was inhibited in the resistance group. ssGSEA showed a significantly lower immune status in the ATRX-Low group compared to the ATRX-High group. Furthermore, the peaks of H3K9me3 ChIP-seq on the four genes were higher in normal tissues than in BC tissues. Notably, the frequency of ATRX mutation was higher than BRCA in BC. Moreover, depressed ATRX revealed worse overall survival and disease-free survival in the human epidermal growth factor receptor 2 (HER2)-/hormone receptor (HR)+ BC. Additionally, depressed ATRX predicted poor results for patients who underwent endocrinotherapy or chemotherapy in the HER2-/HR+ BC subgroup. A nomogram based on ATRX, TILs and ER exhibited a significantly accurate survival prediction ability. Importantly, overexpression of ATRX significantly inhibited the IC50 of the three first-line drugs on MCF-7 cell. Thus, ATRX is an efficient predictive biomarker for endocrinotherapy and chemotherapy resistance in HER2-/HR+ BC and acts by suppressing the AR, GLI3 and GATA2 transcriptional network.

OBJECTIVE: Hepatitis B virus (HBV) spliced variants are associated with viral persistence or pathogenicity. Hepatitis B doubly spliced protein (HBDSP), which has been previously reported as a pleiotropic transactivator protein, can potentially serve as an HBV virulence factor. However, the underlying mechanisms of HBDSP in HBV-associated liver diseases remain to be elucidated. In this study, we revealed that HBDSP promotes cellular apoptosis and induces wt-p53-dependent apoptotic signaling pathway in wt-p53 hepatocellular cells by transactivating p53 transcription, and increases the release of HBV progeny. Therefore, HBDSP may promote the HBV particles release through wt-p53-dependent hepatocellular apoptosis. Our findings suggest that blocking HBDSP-induced wt-p53-dependent apoptosis might have therapeutic values for chronic hepatitis B.

Antiphospholipid syndrome (APS) is a group of clinical syndromes of thrombosis or adverse pregnancy outcomes caused by antiphospholipid antibodies, which increase the incidence of in vitro fertilization failure in patients with infertility. However, the common mechanism of repeated implantation failure (RIF) with APS is unclear. This study aimed to search for potential diagnostic genes and potential therapeutic targets for RIF with APS.
To obtain differentially expressed genes (DEGs), we downloaded the APS and RIF datasets separately from the public Gene Expression Omnibus database and performed differential expression analysis. We then identified the common DEGs of APS and RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and we then generated protein-protein interaction. Furthermore, immune infiltration was investigated by using the CIBERSORT algorithm on the APS and RIF datasets. LASSO regression analysis was used to screen for candidate diagnostic genes. To evaluate the diagnostic value, we developed a nomogram and validated it with receiver operating characteristic curves, then analyzed these genes in the Comparative Toxicogenomics Database. Finally, the Drug Gene Interaction Database was searched for potential therapeutic drugs, and the interactions between drugs, genes, and immune cells were depicted with a Sankey diagram.
There were 11 common DEGs identified: four downregulated and seven upregulated. The common DEG analysis suggested that an imbalance of immune system-related cells and molecules may be a common feature in the pathophysiology of APS and RIF. Following validation, MARK2, CCDC71, GATA2, and KLRC3 were identified as candidate diagnostic genes. Finally, Acetaminophen and Fasudil were predicted as two candidate drugs.
Four immune-associated candidate diagnostic genes (MARK2, CCDC71, GATA2, and KLRC3) were identified, and a nomogram for RIF with APS diagnosis was developed. Our findings may aid in the investigation of potential biological mechanisms linking APS and RIF, as well as potential targets for diagnosis and treatment.

Endometrial cancer (EC) is a reproductive system disease that occurs in perimenopausal and postmenopausal women. However, its etiology is unclear. Melatonin (MT) has been identified as a therapeutic agent for EC; however, its exact mechanism remains unclear. In the present study, we determined that GATA-binding protein 2 (GATA2) is expressed at low levels in EC and regulated by MT. MT upregulates the expression of GATA2 through MT receptor 1A (MTNR1A), whereas GATA2 can promote the expression of MTNR1A by binding to its promoter region. In addition, in vivo and in vitro experiments showed that MT inhibited the proliferation and metastasis of EC cells by upregulating GATA2 expression. The protein kinase B (AKT) pathway was also affected. In conclusion, these findings suggest that MT and GATA2 play significant roles in EC development.

暂无摘要。