Acute leukemia, the most common cancer in childhood, affects children's health severely, whereas the pathogeny and mechanism have not been elucidated clearly yet. As many studies showed, it has been found that transformation of cytogenetics plays a crucial role in leukemia development, and is frequently involved in the transforming action of aml1 gene, one of which is essential for regulation of normal hematogenesis. Moreover, in children acute leukemia, more than one third children with acute leukemia can be detected with dysfunction of the aml1 gene. Our findings highlight the translocation of aml1 gene in children acute leukemia, indicating its mechanism, especailly provide a new target for clinical diagnosis and therapy. In this review, the structure and function of aml1 gene, the abnormality of aml1 gene in acute lymphocytic leukemia, abnormality of aml1 gene in acute myeloid leukemia and so on were summarized.
Child ; Core Binding Factor Alpha 2 Subunit ; genetics ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics

Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; Humans ; Leukemia, B-Cell ; genetics

OBJECTIVE: To explore the rate and distribution of Runt- related transcription factor 1 (RUNX1) gene mutations in patients with acute myeloid leukemia (AML) and the correlation of these mutations with the clinical characteristics and survival outcomes of the patients. METHODS: The genomic DNA extracted from the bone marrow of 158 patients with newly diagnosed AML for PCR amplification of RUNX1 gene and sequence analysis to identify the mutations. The mutations of ASXL1, DNMT3A, TET2, FLT3, CEBPA, NPM1, IDH2, NRAS and c-KIT genes were also examined to analyze their association with RUNX1 gene mutations. RESULTS: Among the 158 AML patients, 19 (12.0%) were found to have RUNX1 mutations in A166G (9 cases), A142T (6 cases) and A162L (4 cases). RUNX1 mutations were more frequent in elderly patients ( CONCLUSIONS RUNX1 gene mutations are associated with an adverse prognosis of patients with AML.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; Remission Induction

Objective: To explore the expression of Runt-related transcription factor 1 (RUNX1) in nasal polyps (NPs) tissues and the potential role on apoptosis of primary human nasal epithelial cells (pHNECs) in NPs. Methods: The expression level of RUNX1 in NPs tissues was determined by Western blot (WB) and immunohistochemical staining (IHC). In vitro, TNF-α (20 ng/ml) was used to stimulate pHNECs to establish the apoptosis injury model. Hoechst staining was performed to observe pHNECs apoptosis by kit. Subsequently, quantitative real-time PCR (qRT-PCR) and WB were utilized to detect the expression of apoptosis-related proteins B-cell lymphoma-2 (BCL-2), BCL2-associated X (BAX) and cysteinyl aspartate specific proteinase-3 (Caspase-3) to assess the level of apoptosis. The plasmid of sh-RUNX1-6 was transfected into the pHNECs apoptosis model, then the effect of RUNX1 silence on apoptosis was evaluated by WB and flow cytometry. Statistical analysis was performed by the SPSS 19.0 and GraphPad Prism5 software. Results: The expression of RUNX1 in NPs tissue was significantly higher than that in inferior turbinates, and the difference was statistically significant (0.274±0.042 vs 0.110±0.027, t=9.675, P<0.05). Compared with the inferior turbinates, BAX and Caspase-3 expressions were increased whereas BCL-2 was decreased in NPs, and the differences were statistically significant (BAX 0.346±0.032 vs 0.302±0.037, Caspase-3 0.228±0.061 vs 0.158±0.065, BCL-2 0.090±0.047 vs 0.276±0.057, t value was 2.680, 2.361 and 7.575, respectively, all P<0.05). The expression levels of RUNX1 and apoptosis in pHNECs increased in a time-dependent manner after TNF-α exposure (P<0.05). Plasmid of sh-RUNX1-6 transfected silenced the expression of RUNX1 in pHNECs treated by TNF-α. After silencing RUNX1 in pHNECs apoptosis model, the protein levels of BAX and Caspase-3 were decreased, while the expression of BCL-2 was increased, the rate of apoptosis was decreased (P<0.05). Conclusions: RUNX1 is increased in NPs. Silencing RUNX1 can inhibit the apoptosis and reduce cell inflammatory damage of pHNECs induced by TNF-α.
Apoptosis ; Core Binding Factor Alpha 2 Subunit/genetics* ; Epithelial Cells ; Humans ; Nasal Polyps ; Turbinates

OBJECTIVE: To study the clinical features and prognosis of core binding factor acute myeloid leukemia (CBF-AML) in children. METHODS: A retrospective analysis was performed from the chart review data of children who were newly diagnosed with CBF-AML in the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from August 2009 to November 2015. According to the type of fusion gene, the children were divided into CBFB-MYH11 and AML1-ETO groups. Clinical features and prognosis were analyzed and compared between the two groups. RESULTS: A total of 91 children with CBF-AML were enrolled in this study, among whom there were 74 (81%) in the AML1-ETO group and 17 (19%) in the CBFB-MYH11 group. Additional chromosomal abnormalities were observed in 38 children (42%), and deletion of sex chromosome was the most common abnormality and was observed in 28 children (31%). After the first course of induction treatment, the complete remission rate was 97% (88/91), the recurrence rate was 29% (26/91), the 5-year event-free survival (EFS) rate was 65%±6%, and the 5-year overall survival (OS) rate was 75%±5%. There were no significant differences between the AML1-ETO and CBFB-MYH11 groups in 5-year EFS rate (62%±7% vs 77%±11%, P>0.05) or 5-year OS rate (72%±6% vs 88%±9%, P>0.05). CONCLUSIONS AML1-ETO is the main type of fusion gene in children with CBF-AML, and deletion of sex chromosome is the most common type of additional chromosomal abnormalities. Children with CBF-AML often have a good prognosis, and the children with AML1-ETO have a similar prognosis to those with CBFB-MYH11.
Child ; Core Binding Factor Alpha 2 Subunit ; Core Binding Factors ; Humans ; Leukemia, Myeloid, Acute ; Oncogene Proteins, Fusion ; Prognosis ; RUNX1 Translocation Partner 1 Protein ; Retrospective Studies

RUNX1, also called AML1, is a member of RUNX transcriptional factor family, and also is the most frequent target for chromosomal translocations in leukemia. RUNX1 is a very important transcription factor, can enhance or repress the expressions of many hematopoiesis related genes. RUNX1 may receive a series of post-translational modifications, and the activity of RUNX1 can be affected by these post-translational modifications, thus RUNX1 regulates the differentiation, apoptosis and self-renewal of hematopoietic cells. This article reviews the role of RUNX1 in the pathogenesis of leukemia mainly including its target genes, transcriptional mechanism and post-translational modifications.
Core Binding Factor Alpha 2 Subunit ; genetics ; Epigenesis, Genetic ; Humans ; Leukemia ; genetics ; metabolism ; Protein Processing, Post-Translational

OBJECTIVE: To investigate whether cell preservation solution can prolong the survival time of leukemia cells and increase the survival rate, so as to improve the detection rate of central nervous system leukemia. METHODS: Kasumi cells were added into cerebrospinal fluid (CSF) supernatant with or without cell preservation solution to compare cell viability and biological characteristics at different time point. Wright Giemsa staining was used to compare cell morphology; cell counting, CCK-8 method, and trypan blue staining were used to compare the cell number, and flow cytometry was used to compare the cell viability. The expression of AML-ETO tumor fusion gene was detected by fluorescence quantitative RT-PCR. RESULTS: At different time points (8 h and 24 h), the survival, molecular biological characteristics and RT-PCR result of the cells in CSF with cell preservation solution were significantly better than those in normal cerebrospinal fluid. CONCLUSION Cell preservation solution can effectively improve the survival time and survival rate of leukemic cells, thereby increase the detection rate of CNS leukemia.
Central Nervous System Neoplasms ; Core Binding Factor Alpha 2 Subunit ; Humans ; Leukemia ; RUNX1 Translocation Partner 1 Protein

OBJECTIVE: To investigate the incidence of Runt-related transcription factor 1 (RUNX1) gene and its associated gene mutations in patients with acute myeloid leukemia (AML), and analyze its clinical characteristics and prognosis. METHODS: The genomic DNA-PCR method was used to detect the exon of RUNX1 gene, and the gene mutations were analyzed by genetic sequencing. NPM1, DNMT3A, FLT3-ITD, IDH1/2, K/N-RAS, CEPBA, TET2, and WT1 co-mutations were also detected. Patients were followed up to determine efficacy and prognosis. RESULTS: Among 171 patients, the RUNX1 gene mutation was detected in 17 cases, and the mutation rate was 9.9%. The type of RUNX1 gene mutation was 9 missense mutations, 4 frameshift mutations, and 4 nonsense mutations. The peripheral blood leukocyte count of the patients in mutation group was 3 (1-101) ×10 CONCLUSION AML patients with RUNX1 gene mutation shows unique clinical and biological characteristics, RUNX1 mutation can be regarded as a molecular marker of poor prognosis in AML patients.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Karyotype ; Leukemia, Myeloid, Acute/genetics* ; Leukocytes, Mononuclear ; Mutation ; Nucleophosmin

Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.
Core Binding Factor Alpha 2 Subunit/metabolism* ; DNA Methylation ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Promoter Regions, Genetic

OBJECTIVETo investigate the effects of AML1B and AML1/ETO fusion gene on the transcription activity of TSC1 and TSC2 promotor and to explore its role in leukemogenesis.

METHODSThe luciferase reporter plasmids of TSCs gene promoter containing a AML1 binding site were constructed, and cotransfected into CV-1 cells with AML1B or AML1/ETO expression plasmids separately. The transactivity of TSCs gene promoter was assayed by luminometer.

RESULTSAML1B exhibited a transactivity to TSC2 gene promoter in a dosage-dependant manner, but showed no significant transactivity to TSC1's. The transactivity to TSC2 gene promoter showed 8.55 fold increase as companed with control group at 75 ng of pCMV5-AML/B. AML1/ETO showed a significant transactivity to TSC1, but no transactivity to TSC2's. However, AML1/ETO antagonized the effect of AMLlB to TSC2 gene promoter.

CONCLUSIONAML1B and AML1/ETO can regulate the transcription of TSC genes.

Binding Sites ; Core Binding Factor Alpha 2 Subunit ; genetics ; Humans ; Oncogene Proteins, Fusion ; genetics ; Plasmids ; Promoter Regions, Genetic ; Transcription Factors ; genetics ; Transcriptional Activation