Résumé
This study was purpose to analyze the frequency and of isocitrate dehydrogenase 2 (IDH2) gene mutation in acute myeloid leukemia (AML) and its clinic significance. The multiplex polymerase chain reaction (PCR) and sequencing were performed to screen 192 AML patients for exon 4 of the IDH2 gene. FLT3, NPM1, CEBPA, c-kit and WT1 mutations were also included in analysis. The results showed that IDH2 mutation was found in 14 (7.29%) of 192 patients. There were 9 AML patients with R140Q mutation, 1 patient with R140W mutation, and 1 patient with R172K mutation. IDH2 aberrations significantly more were detected in French-American-British (FAB) M5 (P < 0.005) than other types. There was no statistical difference in age, sex, WBC, platelet count, bone marrow blasts count, hemoglobin as compared with IDH2 wild-type. For immunotype analysis, IDH2 mutation patients were more likely to express CD34 and CD13, less CD36. IDH2 mutation combined with FLT3/ITD mutation was found in 7 cases, with CEBPA mutation in 4 cases, with NPM1 mutation in 4 cases, with Dnmt3a mutation in 5 cases, neither with c-kit, IDH1 or WT1 mutation for no one, which revealed a significant interaction between IDH2 mutation and the FLT3/ITD positive genotype, Dnmt3a mutated, and IDH1 wild-type. IDH2 mutation was detected in 5 (8.47%) of 59 CN-AML. There was no significant difference of IDH2 mutation incidence between the normal and abnormal karyotype. The CR rate was higher in IDH2 R140 mutated patients than wild-type ones, but there was no significant in the two group. It is concluded that the rate of IDH2 mutation is 7.29% in Chinese AML patients and 7.81% in CN-AML. IDH2 mutation is significantly associated with AML-M5, FLT3/ITD, Dnmt3a, IDH1 wild-type and fusion gene wild-type, but not with age, leucocyte and platelet counts in peripheral blood, karyotype, NPM1, CEBPA, c-kit or WT1 mutation. And IDH2 R140 mutation has no impact on CR rate.
Sujets)
Adolescent , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Asiatiques , Génétique , DNA (cytosine-5-)-methyltransferase , Génétique , Génotype , Isocitrate dehydrogenases , Génétique , Caryotypage , Leucémie aigüe myéloïde , Épidémiologie , Génétique , Mutation , Protéines nucléaires , Génétique , Pronostic , Induction de rémission , Protéines WT1 , Génétique , Tyrosine kinase-3 de type fms , GénétiqueRésumé
Patients with FLT3-ITD (mut) /NPM1 (-) cytogenetically normal acute myeloid leukemia (CN-AML), as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD (mut) /NPM1 (-) CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells. The FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary generation models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully established xenotransplantation model of human FLT3-ITD (mut) /NPM1 (-) CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.
Sujets)
Adolescent , Adulte , Sujet âgé , Animaux , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Lignée cellulaire tumorale , Modèles animaux de maladie humaine , Leucémie aigüe myéloïde , Anatomopathologie , Chirurgie générale , Souris de lignée NOD , Souris knockout , Souris SCID , Transplantation tumorale , Méthodes , Protéines nucléaires , Génétique , Transplantation hétérologue , Méthodes , Tyrosine kinase-3 de type fms , GénétiqueRésumé
Patients with FLT3-ITD (mut) /NPM1 (-) cytogenetically normal acute myeloid leukemia (CN-AML), as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD (mut) /NPM1 (-) CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells. The FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary generation models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully established xenotransplantation model of human FLT3-ITD (mut) /NPM1 (-) CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.
Résumé
This study was purposed to detect the mutation of isocitrate dehydrogenase 1 (IDH-1) gene in patients with acute myeloid leukemia (AML) and to explore its clinical significance. The genomic DNA was extracted from mononuclear cells (MNC) of bone marrow or peripheral blood in 205 adult AML patients, the exon 4 of IDH1 gene was amplified by PCR, then the sequencing and comparison were performed. The results showed that IDH1 mutation was detected in 9 (4.39%) of 205 AML patients. There were 6 cases of R132H mutation, 1 of R132L mutation, 1 of R132G mutation and 1 of R132S mutation. Significantly more IDH1 aberrations were detected in AML-M2 (P = 0.002) than other types. And the 9 patients with IDH1 mutation were characterized by low platelet count which was lower than patients with wild type IDH1 (P = 0.003). IDH1 mutation combined with FLT3/ITD mutation was found in 5 cases, c-kit mutation in 1, NPM1 mutation in 2, and IDH1 mutation with CEBPA or WT1 mutation was not found, which revealed a significant interaction between IDH1 mutation and the FLT3/ITD positive genotype or the CEBPA wild-type. IDH1 mutation were detected in 4 of 71 (5.63%) CN-AML. There was no significant difference of IDH1 mutation incidence between the normal and abnormal karyotypes. It is concluded that the rate of IDH1 mutation was 4.39% in Chinese AML patients. IDH1 mutation is significantly associated with AML-M2, lower platelet counts in peripheral blood, FLT3/ITD mutation and CEBPA wild-type, but not with age, white blood cell count in peripheral blood, karyotype, NPM1, c-kit or WT1 mutation.
Sujets)
Adolescent , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Analyse de mutations d'ADN , Isocitrate dehydrogenases , Génétique , Caryotypage , Leucémie aigüe myéloïde , Génétique , MutationRésumé
<p><b>OBJECTIVE</b>To probe into the method for effectively increasing complete abortion rate of medicine-induced abortion and observe pathological changes.</p><p><b>METHODS</b>Two hundred cases were randomly divided into an observation group and a control group, 100 cases in each group. The observation group were treated by acupuncture at Hegu (LI 4), Sanyinjiao (SP 6), Neiguan (PC 6) and Kunlun (BL 60), and the control group were not treated by acupuncture. The abortion rate, bleeding condition, adverse reaction and pathological changes were observed in the two groups.</p><p><b>RESULTS</b>The complete abortion rate was 96.0% in the observation group, better than 88.0% in the control group (P < 0.05). There were significant differences between the two groups in bleeding time and pathological changes (P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture can increase complete abortion rate of medicine-induced abortion, with shorter bleeding time and less residual villus.</p>
Sujets)
Femelle , Humains , Grossesse , Avortement provoqué , Thérapie par acupunctureRésumé
Objective To study the incidence of vitamin K deficiency in low-birth weight premature infants and its relationship with intraventricular hemorrhage.Methods We use emzymoimmunoelectrophoresis to detect prophrombin protein precursors(PIVKA-Ⅱ) in vein blood in premature infants