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OBJECTIVE@#To characterize the mutational profile of patients with core-binding factor acute myeloid leukemia (CBF-AML).@*METHODS@#A total of 81 acute myeloid leukemia patients were recruited, which included 36 cases of CBF-AML and 45 cases of cytogenetically normal acute myeloid leukemia (CN-AML) . Mutations of FLT3-ITD, FLT3-TKD, NPM1, c-KIT, NRAS, KRAS, TET2, IDH1/2, RUNX1, DNMT3A, GATA2, ASjXL1, TP53, PTPN11, JAK2V617F, SETBP1 and CEBPA genes were simultaneously detected by DNA-based PCR and Sanger sequencing.@*RESULTS@#Over all, mutations were detected in 68 patients (83.9%), with the most common ones including double CEBPA mutations (n=17), followed by NPM1 (n=15), c-KIT (n=11), NRAS (n=10), TET2 (n=9), FLT3-TKD (n=9), FLT3-ITD (n=8), IDH1 (n=7), RUNX1 (n=7), KRAS (n=7), DNMT3A (n=6), IDH2 (n=4), and GATA2 (n=4) mutations. AML1-ETO and CBFβ-MYH11 fusions were present in 21 and 15 patients, respectively. Coexistence of ≥2 mutations was more common in CN-AML comparing with CBF-AML. The mutation rate of NPM1, FLT3-ITD, DNMT3A, IDH1 and CEBPA double mutations were higher in patients with CN-AML. NRAS, c-KIT and KRAS mutations were identified more frequently in patients with CBF-AML (P<0.05). Based on the function, aberration of genes involved in DNA methylation, NPM1 proteins and transcription predominated in CN-AML, while tyrosine kinase receptor signaling and RAS pathways have predominated in CBF-AML.@*CONCLUSION@#The genomic landscape of CBF-AML patients has differed from that of CN-AML patients. Synergy of fusion genes with particular mutations may impact the clinical phenotype and prognosis of patients.
Subject(s)
Humans , Core Binding Factors , Genetics , DNA Mutational Analysis , Leukemia, Myeloid, Acute , Genetics , Mutation , PrognosisABSTRACT
AIM:To investigate the role of phospholipase C epsilon 1 ( PLCE1 ) in modulating the apoptotic mechanism in lung adenocarcinoma A 549 cells.METHODS:PLCE1 inhibitor U-73122 was used to suppress the expres-sion of PLCE1.The expression of PLCE1 and p53 in A549 cells was evaluated by quantitative real-time PCR and Western blotting.Apoptosis was assessed by flow cytometry .RESULTS:A549 cells expressed high level of PLCE1 and low level of p53.Inhibition of PLCE1 markedly increased the expression of p 53, and increased the apoptosis of A 549 cells.CON-CLUSION:PLCE1 suppresses apoptosis of A549 cells via inhibiting the expression of p53.
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Aim To investigate the role of phospho-lipase C epsilon 1 ( PLCE1 ) in modulating the apoptot-ic mechanism in esophageal cancer ( Eca ) cells. Methods Eca cell lines, OE33 and CP-C cells were cultured to assess the expression of PLCE1 . siRNA suppress expression of PLCE1 . The expression of PLCE1 and p53 was evaluated by quantitative real time PCR and Western blot. Methylation analyses of p53 were performed by bisulfite conversion of genomic DNA. Apoptosis was assessed by flow cytometry. Results OE33 and CP-C cells expressed high levels of PLCE1 . Knockdown of PLCE1 markedly increased the expression and hypomethylation of p53 , and in-creased the frequency of apoptosis. Conclusion PLCE1 suppresses apoptosis of Eca cells via promoting p53 promoter methylation and inhibiting expression of p53 .
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<p><b>OBJECTIVE</b>To explore the mechanism of NK cell dysfunction in patients with multiple myeloma (MM).</p><p><b>METHODS</b>The expression of inhibitory receptors (CD158a and CD158b) and activating receptors NKG2D and NCRs (NKp30, NKp44 and NKp46) on CD3-CD56+NK cell of 13 MM patients and 30 healthy controls were analyzed by flow cytometry. The concentration of soluble NKG2D ligands (MICA, MICB, ULBP1, ULBP2 and ULBP3) in serum was detected by enzyme- linked immunosorbent assay (ELISA), and the cytotoxicity of NK cell against MM cell line by flow cytometry.</p><p><b>RESULTS</b>There are no significant differences of percentage and absolute number of NK cells, and the expression level of CD158a and CD158b between MM patients and healthy individuals (P>0.05). No NKp44 expression was detected on fresh isolated NK cells from both groups. There is no difference in inhibitor receptors expression between MM patients and healthy individuals but the expression of NKG2D, NKp30 and NKp46 on NK cells were higher in MM patients as compared with that in healthy individuals. The concentration of soluble NKG2D ligands in serum was higher in MM patients as compared with that in healthy individuals (P<0.05). Cultured healthy individual's NK cells with MM patient's serum could significantly decrease its cytotoxicity against MM cell line U266 cells [(38.5 ± 6.5) % vs (25.4 ± 5.9)%, P=0.044］.</p><p><b>CONCLUSION</b>The higher level of soluble NKG2D ligands in serum may be the mechanism of NK cell dysfunction in MM patient.</p>