Molecular genomic landscape of myeloid neoplasms in elderly patients / 中华老年医学杂志

Objective:To explore the molecular genetics of myeloid neoplasms in elderly patients.Methods:High-throughput DNA sequencing was performed to detect 49 target gene mutations in 26 patients with acute myeloid leukemia(AML)and 51 patients with myelodysplastic syndrome(MDS). Genomic DNA-PCR and Sanger sequencing were used to detect the mutations of CALR gene exon 9, NMP1 gene exon 12, FLT3-ITD and the two functional domains, TAD and BZIP, in CEBPA.Results:(1)Of the 77 patients enrolled, the overall incidence of gene mutations was 91.0%(71/77), with an average of 2 mutations per patient and an incidence of 42.9% for the coexistence of 3 or more gene mutations(33/77), and the most common genetic mutations were NPM1, U2AF1, RUNX1, TET2, ASXL1, TP53, DNMT3A, IDH2, BCOR, and FLT3-ITD, and the incidence of other genetic mutations was<10%.(2)The incidence of double gene mutations in the AML group was significantly higher than that in the MDS group, and the incidence of≥3 gene mutations in the MDS group was higher than that in the AML group( P<0.05). The AML group was associated with significantly higher incidences of NPM1, FLT3-ITD, and CEBPA double mutations and lower incidences of BCOR and ASXL1 mutations than those in the MDS group(all P<0.05). Functional classification showed that tyrosine kinase receptor gene mutations mainly occurred in the AML group( P=0.004), while chromatin modified gene mutations mainly occurred in the MDS group( P=0.007). (3)Fifty-one cases with MDS were followed up and 9 cases developed leukemia transformation with an average transformation time of 6.5 months during the period, and the conversion rate of patients with RUNX1 and U2AF1 mutations was 44.4%, which was higher than that of other gene mutations. Conclusions:Elderly patients with myeloid neoplasms have unique gene mutation profiles.The types and frequencies of common myeloid tumor gene mutations are different in AML and MDS, and some gene mutations in patients with MDS are related to leukemia transformation.

Characterizing the molecular cytogenetics in acute monocytic leukemia / 中华医学遗传学杂志

OBJECTIVE@#To characterize the molecular genetics of 81 patients with acute monocytic leukemia (AML).@*METHODS@#Fluorescence in situ hybridization (FISH) was employed to detect MLL gene rearrangements. Combined mutations of 17 genes were detected by DNA-based PCR and Sanger sequencing.@*RESULTS@#Sixty seven patients were found to harbor at least one mutation. The most commonly mutated gene was NPM1 (n=18), which was followed by FLT3-ITD (n=16), NRAS (n=16), DNMT3A (n=15), TET2 (n=12), RUNX1 (n=11) and KRAS (n=9). Based on the functions of mutated genes, the most frequently involved genes were those involved in DNA methylation (38.27%), tyrosine kinase receptor signaling (32.1%), transcription regulation (28.4%), and RAS pathway (24.7%). Single gene mutation predominated in patient with cytogenetic abnormalities, while coexistence of 2 mutations have predominated in patient with normal cytogenetic findings. Stratified by cytogenetic findings, patients with single gene mutations (intermediate-risk group) had significantly higher complete remission (CR) rates than those with ≥2 gene mutations (unfavorable-risk group) (91.7% vs. 57.6% , 87.5% vs. 25.0%, P =0.0319, 0.0117, respectively).@*CONCLUSION@#Over 80% of AML patients were found to harbor at least one mutation. Their clinical phenotype and prognosis may be impacted by the synergy of MLL gene rearrangement and multiple mutations. For patients under the same risk stratification, the number of mutations is reversely correlated with the CR rate.

Characterization of mutational pattern of patients with core-binding factor acute myeloid leukemia / 中华医学遗传学杂志

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.

Study of NK cells dysfunction in multiple myeloma patients / 中华血液学杂志

<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>

Study on Treatment of Iron Deficiency Anemia with Shengxuening / 国际中医中药杂志

Objective To observe the therapeutic effect of Shengxuenin(SXN) in treating iron deficiency anemia (IDA).Methods 60 cases with IDA from January 2007 to June 2008 were treated with SXN,2 pellets Tid per os for 30 days.The value of erythlrocyte count (RBC),haematoglobin(Hb),hematocrit(HCT),mean corpuscular volume(MCV).mean corpuscular haematoglobin (MCH),mean corpuscular-hemoglobin concentration (MHCH),Reticulocyte(Ret) was observed at the first week,the second week,the third week and the fourth week of the treatment.Results Reficulocyte count started to increase at the lst week and haematoglobin count started to increase at the 2nd week.Haematoglobin,mean corpuscular volume,mean corpuscular haematoglobin and mean corpuscular-hemoglobin concentration returned to normal at the 4th week.The gastrointestinal side effects of this thempy were fewer than treated with other chalybeate medicines.Conclusion SXN was effective in the treatment of IDA and had little gastrointestinal side effects.