MonoMAC syndrome is a newly discovered immune deficiency syndrome caused by GATA-2 mutation, which is an autosomal dominant genetic disease. MonoMAC syndrome has typical immune cell abnormalities, with severe infection and is prone to develop into a hematological disease. Therapeutics for this disease mainly relies on symptomatic treatment and hematopoietic stem cell transplantation. In this paper, the research advances in clinical manifestations, laboratory tests, pathogenesis, diagnosis and treatment of MonoMAC syndrome are reviewed.
GATA2 Transcription Factor ; genetics ; Humans ; Immunologic Deficiency Syndromes ; genetics ; Monocytes ; pathology ; Mutation ; Mycobacterium Infections ; etiology ; Syndrome

An 11-year-old girl was found to have pale complexion and anemia with gradual aggravation for one year. She was weak in the past and developed pneumonia in the right middle lung 3-5 times per year, which was improved after anti-infective therapy. She and her mother had congenital deaf-mutism. Physical examination showed the appearance of anemia, without bleeding, jaundice, hepatosplenomegaly, or lymph node enlargement. Routine blood test results showed reductions in all three blood cell lines, normocytic anemia, and megaloblastoid change in granulocytic and erythroid cell lines in bone marrow, with no obvious increase in primitive cells or metastatic tumor cells. Whole exome sequencing indicated the presence of a known pathogenic mutation for Emberger syndrome (ES), c.1084C>T (p.Arg362*) in the GATA2 gene. The girl was finally diagnosed with ES, and myelodysplastic syndrome (MDS) progressed to acute myeloid leukemia during follow-up. ES is a rare type of MDS with autosomal dominant inheritance in clinical practice, and it is difficult to make a confirmed diagnosis. ES should be considered for children with unexplained lymphedema and congenital deafness, and gene detection should be performed to make a confirmed diagnosis.
Anemia ; complications ; Child ; Female ; GATA2 Transcription Factor ; Humans ; Lymphedema ; Mutism ; complications ; Myelodysplastic Syndromes

OBJECTIVETo find out how GATA-1 and GATA-2 behave in the bone marrow of patients with Monge's disease.

METHODSThe levels of mRNA in mononuclear cells (MNC) and proteins of GATA-1 and GATA-2 in the bone marrow of patients with Monge's disease and controls were determined by RT-PCR and immune cytolysis chemical method.

RESULTS(1) All patients and controls expressed GATA-1 mRNA (Monge's disease 1.033 +/- 0.146, Control 0.458 +/- 0.076) and GATA-2 mRNA (Monge's disease 0.451 +/- 0.073, Control 0.185 +/- 0.074). All patients expressed both GATA-1 (positive cell counts 77.3 +/- 33.3, positive score 135.4 +/- 75.4) and GATA-2 ( positive cell counts 29.4 +/- 11.4, positive score 48.4 +/- 19.7). All the controls expressed GATA-1 (positive cell counts 18.1 +/- 11.3, positive score 24.2 +/- 13.4) while 12 of 20 controls expressed GATA-2 ( positive cell counts 5.4 +/- 3.0, positive score 7.3 +/- 4.2). The expression of mRNA and proteins of GATA-1 and GATA-2 in Monge's disease were higher than in controls (P < 0.01). (2) There was a positive correlation between GATA-1 and Hb (P < 0.01), as did between mRNA and proteins of GATA-1 and GATA-2. (3) Both the proteins of GATA-1 and GATA-2 located only in the cytoplasm but not the nucleus.

CONCLUSIONSTwo of inherent genes, GATA-1 and GATA-2 which were expressed at higher levels in patients with Monge's disease than in controls might play significant roles in the pathogenesis of Monge's disease.

Adult ; Altitude Sickness ; metabolism ; GATA1 Transcription Factor ; metabolism ; GATA2 Transcription Factor ; metabolism ; Humans ; Male ; Polycythemia ; metabolism ; RNA, Messenger ; metabolism

This study was aimed to investigate the effect of GATA-2 over-expression on function of mouse fetal liver hematopoietic stem cells. GATA-2 was introduced into mouse fetal liver cells via retrovirus mediated transduction with GFP as a detecting marker. Flow cytometry, colony-forming assay and cell cycle assay were used to detect the biologic changes of these retrovirus infected mouse fetal liver hematopoietic stem cells. The results showed that GATA-2 over-expression increased the Lin(-)Sca1(+)C-Kit(+) (LSK) population dramatically. Cell cycle of LSK cells didn't show abnormal, while colony forming ability decreased significantly. These data indicated that GATA-2 over-expression inhibited definitive differentiation of mouse fetal liver hematopoietic stem cells. It is concluded that over-expression of GATA-2 can significantly raise the LSK cell proportion in mouse fetal liver and inhibit the differentiation capability, the underlying mechanisms may be related to up-regulation of Hes-1, which may lead to the blocking of cell differentiation at the stem/progenitor cell stage.
Animals ; Cell Differentiation ; Cells, Cultured ; Female ; GATA2 Transcription Factor ; genetics ; Hematopoietic Stem Cells ; cytology ; Liver ; cytology ; Male ; Mice ; Mice, Inbred C57BL

Objective: To clarify the prevalence, clinical features and molecular characteristics of germline GATA2 mutations in pediatric primary myelodysplastic syndromes (MDS) . Methods: Next-generation sequencing technology was used to detect mutations in GATA2 and other myeloid malignancy genes in 129 children with primary MDS from Jan. 2007 to Jan. 2018. The relationship between genotypes and phenotypes was analyzed. Results: Germline GATA2 mutations accounted for 8.5% (11/129) of all primary MDS cases, and 14.0% (11/50) of MDS with excess blasts (MDS-EB) and acute myeloid leukaemia with myelodysplasia-related changes (AML-MRC) . Compared with GATA2 wild-type patients, GATA2 mutated patients were older at diagnosis[8 (1-16) years old vs 6 years old (range: 1 month old-18 years old) , P=0.035]and higher risk of monosomy 7 (72.7%vs 5.2%, P<0.001) and classified into MDS-EB and AML-MRC compared with refractory cytopenia of childhood (RCC) (63.6%vs 36.4%, P=0.111) . The multivariate analysis showed SETBP1 mutation (P=0.041, OR=9.003, 95%CI 1.098-73.787) and isolated monosomy 7 (P=0.002, OR=24.835, 95%CI 3.305-186.620) were significantly associated with germline mutated GATA2. Overall survival (OS) and outcomes of hematopoietic stem cell transplantation (HSCT) were not influenced by GATA2 mutational status. Conclusions: Our data identify germline GATA2 mutations have a high prevalence in older pediatric patients with monosomy 7, and high risk of progression into advanced MDS subtypes. GATA2 mutation status does not affect OS in pediatric primary MDS.
Adolescent ; Child ; Child, Preschool ; GATA2 Transcription Factor/genetics* ; Germ-Line Mutation ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes/genetics*

OBJECTIVETo investigate the effect of simulated microgravity on erythroid differentiation of K562 cells and explore the possible mechanism.

METHODSThe fourth generation rotating cell culture system was used to generate the simulated microgravity environment. Benzidine staining was used to evaluate the cell inhibition rate, and real-time quantitative PCR (qRT-PCR) was used to detect GATA-1, GATA-2, Ets-1, F-actin, β-Tubulin and vimentin mRNA expressions. The changes of cytoskeleton were observed by fluorescence microscopy, and Western blotting was employed to assay F-actin, β-tubulin and vimentin protein expression levels.

RESULTSBenzidine staining showed that simulated microgravity inhibited erythroid differentiation of K562 cells. K562 cells treated with Hemin presented with increased mRNA expression of GATA-1 and reduced GATA-2 and Ets-1 mRNA expressions. Simulated microgravity treatment of the cells resulted in down-regulated GATA-1, F-actin, β-tubulin and vimentin mRNA expressions and up-regulated mRNA expressions of GATA-2 and Ets-1, and reduced F-actin, β-tubulin and vimentin protein expressions. Exposure to simulated microgravity caused decreased fluorescence intensities of cytoskeletal filament F-actin, β-tubulin and vimentin in the cells.

CONCLUSIONSimulated microgravity inhibits erythroid differentiation of K562 cells possibly by causing cytoskeleton damages to result in down-regulation of GATA-1 and up-regulation of GATA-2 and Ets-1 expressions.

Actins ; metabolism ; Cell Differentiation ; Down-Regulation ; GATA1 Transcription Factor ; metabolism ; GATA2 Transcription Factor ; metabolism ; Hemin ; pharmacology ; Humans ; K562 Cells ; Proto-Oncogene Protein c-ets-1 ; metabolism ; Tubulin ; metabolism ; Up-Regulation ; Vimentin ; metabolism ; Weightlessness Simulation

iASPP can prompt the cell proliferation and inhibit the apoptosis of many cells. There are putative binding sites of transcription factor GATA-2 upstream of iASPP transcription start site. GATA-2 plays an important role in the proliferation and differentiation of hematopoietic stem cells (HSC) and progenitors. This study was aimed to explore the role of GATA-2 protein in iASPP gene transcription. Firstly, the expression of iASPP and GATA-2 protein in some leukemia cell lines was detected by Western blot. Second, The expressive vector of pCMV5-GATA2 and the luciferase reporter vectors containing possible binding sites of GATA-2 were constructed and co-transfected into HEK293 and CV-1 cells. Then the luciferase activity was assayed by luminometer. Also, ChIP assays were performed to further confirm the specific binding of GATA-2 to iASPP promoter. The results showed that GATA-2 was overexpressed in most cell lines with high level of iASPP. GATA-2 exhibited a significant effect on luciferase activity of reporter gene iASPP and in a dose-dependant manner. The relative luciferase activity was up-regulated to about two-fold of the empty vector control when the transfection dose of pCMV5-GATA2 plasmid was increased to 100 ng. While the effect was more significant in CV-1 cells and showed a 6.7-fold increase. The ChIP assay demonstrated the in vivo specific binding of GATA-2 to iASPP. The binding sites of GATA2 were located between nt -361 ∼ -334 in upstream of iASPP gene transcription start site. It is concluded that transcription factor GATA-2 can bind with the cis-regulatory region of the iASPP promoter and up-regulate iASPP expression.
Animals ; Cell Line ; Cercopithecus aethiops ; GATA2 Transcription Factor ; genetics ; Gene Expression Regulation, Leukemic ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; K562 Cells ; Repressor Proteins ; genetics ; Transcription, Genetic ; Transcriptional Activation ; Transfection

OBJECTIVETo explore the expression of NF-E1b in colorectal cancer tissues and its association with various clinicopathological parameters and prognosis of the patients.

METHODSClinicopathological and follow-up data of 168 colorectal cancer patients undergoing radical operation at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from 2005 to 2012 were retrospectively analyzed, including 96 males and 72 females, with mean age of (57.8±11.2) years. The expression of NF-E1b protein was detected in samples of 168 resected colorectal cancer tissues and 45 adjacent non-cancerous tissues by immunohistochemistry. The expression rates of NF-E1b were compared among different clinicopathological features. Moreover, the association between NF-E1b expression and prognosis was analyzed.

RESULTSThe expression of NF-E1b protein located mainly in cytoplasm. Positive rate of NF-E1b expression in adjacent non-cancerous tissues was 17.8% (8/45), which was obviously lower than 67.9%(114/168) of cancer tissues with significant difference (χ(2)=36.376, P=0.000). Clinicopathological parameters analysis suggested that the expression level of NF-E1b in cancer tissues was associated with age (χ(2)=4.862, P=0.030), TNM staging (χ(2)=10.969, P=0.002), lymph node metastasis (χ(2)=7.390, P=0.008) and distal metastasis (χ(2)=17.887, P=0.000). The median follow-up time was 23(1-77) months. The overall 5-year survival of this cohort was 33.3%. Colorectal cancer patients with high levels of NF-E1b expression showed a worse overall survival compared with those with low levels of NF-E1b expression (18.4% vs. 56.6%, P=0.000). Univariate Cox regression analysis showed that tumor location (P=0.034), tumor size (P=0.003), TNM staging (P=0.000), depth of tumor invasion (P=0.009), lymph node metastasis (P=0.000), distant metastasis (P=0.000) and NF-E1b expression level (P=0.001) were associated with the prognosis of colorectal cancer patients. Multivariate Cox regression analysis revealed that tumor diameter >4 cm (HR=2.193,95% CI:1.334 to 3.603, P=0.002), distant metastasis (HR=2.064, 95% CI:1.160 to 3.672, P=0.014) and high NF-E1b expression (HR=1.994,95% CI:1.068 to 3.724, P=0.030) were independent risk factors of predicting poor prognosis of colorectal cancer patients.

CONCLUSIONSNF-E1b expression up-regulates in colorectal cancer tissues. High expression of NF-E1b is associated with poor prognosis of colorectal cancer patients. NF-E1b may serve as a potential target of the treatment for colorectal cancer.

Aged ; Biomarkers, Tumor ; metabolism ; Colorectal Neoplasms ; diagnosis ; metabolism ; Digestive System Surgical Procedures ; Female ; GATA2 Transcription Factor ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Up-Regulation

No abstract available.
DNA Mutational Analysis ; Female ; *Frameshift Mutation ; GATA2 Transcription Factor/*genetics ; Genetic Predisposition to Disease ; Hearing Loss, Sensorineural/diagnosis/genetics ; Humans ; Lymphedema/diagnosis/*genetics ; Myelodysplastic Syndromes/diagnosis/*genetics ; Phenotype ; Republic of Korea ; Young Adult

In order to investigate expressions of transcription factor GATA-1 and GATA-2 genes in the bone marrow stromal cells (BMSCs) from patients with leukemia or normal controls, bone marrow stromal cells from 34 normal cases and 42 cases with leukemia were cultured long-term in vitro. Nonadherent cells (bone marrow hematopoietic cells) and amplified adherent cells (BMSC) were collected separately. Expressions of GATA-1 and GATA-2 genes were analyzed by using RT-PCR-ELISA; the semi-quantitative expression levels of GATA genes in the BMSCs from patients with leukemia were compared with normal controls. The results showed that expressions of GATA-1 and GATA-2 genes could be detected in the BMSCs and the bone marrow hematopoietic cells from both normal controls and the cases of leukemia. The expression ratio of GATA-1 in the BMSCs from acute lymphocytic leukemia (ALL) (85.7%) was similar to the normal controls (88.2%), whereas the expression ratios in BMSCs from acute myelocytic leukemia (AML) (55.6%) and chronic myelocytic leukemia (CML) (41.2%) were significant lower than the normal controls (P < 0.05). The rank of expression level of GATA-1 gene in the BMSCs was "ALL>AML>normal>CML". There was no difference in the expression level of GATA-2 gene within the BMSCs from normal controls and patients with leukemia. The ranks of expression levels of GATA-1 and GATA-2 genes in bone marrow hematopoietic cells were "AML>normal>ALL>CML" and "AML>CML>ALL>normal". The dominant expression of GATA-2 gene was found in the BMSCs from AML, CML or normal controls. It is inferred that the expressions of GATA-1 and GATA-2 genes in the BMSCs of normal controls and patients with leukemia may influence the regulation of hematopoiesis in the bone marrow stroma and it is worthy of further study to explore their roles in pathogenesis and development of leukemia.
Adolescent ; Adult ; Aged ; Bone Marrow Cells ; metabolism ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; GATA1 Transcription Factor ; biosynthesis ; genetics ; GATA2 Transcription Factor ; biosynthesis ; genetics ; Gene Expression Regulation, Leukemic ; Humans ; Leukemia ; blood ; pathology ; Male ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction ; Stromal Cells ; metabolism