Dissertation > Excellent graduate degree dissertation topics show

Detect NPM1 and FLT3-ITD Mutation in Acute Myeloid Leukemia and Assess Its Clinical Significance

Author: ChenJianLan
Tutor: LiQingShan
School: Guangzhou Medical College
Course: Department of Hematology
Keywords: NPM1 FLT3-ITD Acute myeloid leukemia Gene mutation
CLC: R733.71
Type: Master's thesis
Year: 2011
Downloads: 19
Quote: 0
Read: Download Dissertation

Abstract


Objective: To establish a high-resolution melting curve (HRM) qualitative detection of newly diagnosed acute myeloid leukemia (AML) patients with NPM1 gene mutations and denaturing high-performance liquid chromatography (DHPLC) technology relative quantitative detection of de novo AML patients with FLT3-ITD gene mutation and analysis mutations in the patient's clinical information, and to explore the relationship between NPM1 and FLT3-ITD gene mutations in AML clinical characteristics, clinical stratified treatment for AML, molecular targeted therapy and prognosis reference index. Method: 1. Using the polymerase chain reaction (PCR) combined with HRM PCR combined with capillary electrophoresis (CE) technology, the sequencing method NPM1 gene mutations detected 103 cases of AML patients, compared to verify the specificity of the PCR combined HRM detect NPM1 gene mutations and sensitivity. Relative quantitative detection of 103 cases of AML patients with FLT3-ITD mutant alleles. DHPLC technology combined with PCR and mutation detection with CE and validation of the method, the final sequenced to verify the mutation presence. 3 of 86 patients with available data of 103 patients with newly diagnosed AML NPM1, FLT3-ITD gene mutation test results and clinical data for analysis, discussion NPM1, FLT3-ITD gene mutation general clinical characteristics of the patients, leukemia immunophenotyping, nuclear type analysis, clinical efficacy and prognostic features. Results: 1. Successfully established PCR combined with HRM technology to detect the AML patients NPM1 gene mutations, achieved 100% specificity and sensitivity. Consistent positive findings sequencing results. The successfully established PCR combined with DHPLC technology relative quantitative detection of gene mutations in AML patients with FLT3-ITD, no significant difference in the quantitative results compared with the the CE Technical quantitative results. Consistent positive rate and sequencing. 3.103 cases of AML patients, 31 patients (30.1%) were detected NPM1 gene mutations. Clinical data of 86 patients, found that patients with normal karyotype AML NPM1 gene mutation detection rate of 47.6%. Were found in the A, B, D three NPM1 gene mutations. 4.103 cases of AML patients, 20 patients (19.4%) were detected in FLT3-ITD gene mutation. 20 cases of mutations in patients with a low proportion of mutations in six cases, moderate proportion of mutations in the eight cases, the high proportion of mutations in six cases. Sequenced and found FLT3-ITD mutant gene was inserted fragment size of 12bp-107bp, are single insert fragment. The clinical data of 86 patients, normal karyotype AML patients with FLT3-ITD mutation detection rate of 26.2%. 5.NPM1 mutation in peripheral blood in patients with high white blood cells was significantly higher than that of wild-type patients (median 21.4 × 109 / L vs 8.4 × 109 / L, P = 0.034), immunophenotyping associated with CD34 low expression (P = 0.022 ). FLT3-ITD mutations in patients with peripheral white blood cells than wild-type patients (median 23.1 × 109 / L vs 9.5 × 109 / L, P = 0.037), mutant bone marrow blast cell percentage higher than the wild-type (median 0.76 vs 0.4, P = 0.023), and and immunophenotyping (P = 0.024) associated with CD7 high expression. 6.NPM1 mutation group compared with the rate of complete remission (CR) of the wild group was no significant difference (P = 0.883) between the first course of chemotherapy, the rate of complete remission (CR1) compared statistical differences (P = 0.042 ). FLT3-ITD mutation group and wild group CR, CR1 was no statistical difference (P = 0.43, P = 0.072). 7.NPM1-/FLT3-ITD-, NPM1 / FLT3-ITD-, NPM1-/FLT3-ITD, NPM1 / FLT3-ITD four groups the proportion was 57.0%, 23.3%, 12.8% and 6.9% CR rate 81.6%, 85%, 54.5% and 66.6%, within one year RR was 42.5%, 17.6%, 50%, 25%, NPM1 / FLT3-ITD-CR rate highest year RR minimum. NPM1-/FLT3-ITD group CR rate the lowest RR highest in a year. Conclusion: PCR combined with HRM can quickly and accurately detect the AML patients NPM1 gene mutations, PCR combined DHPLC accurate quantitative detection of gene mutations in AML patients with FLT3-ITD. NPM1 and FLT3-ITD gene mutation in patients with specific clinical characteristics. NPM1 / FLT3-ITD-best prognosis, NPM1-/FLT3-ITD worst prognosis. NPM1 mutation and FLT3-ITD mutation as a layered treatment of AML can be used as one of the independent indicator of prognosis.

Related Dissertations

  1. Influences of Temperature on SCF/c-kit Prolifertation Pathway and Cell Cycle of Rat Spermatogonial Cells Cultured in Vitro,R698
  2. CHST6 Mutations and Histopathologic Study in Macular Corneal Dystrophy,R772.2
  3. Chinese people early-onset type 2 diabetes , IGT / IFG patients were paired box gene 6 gene mutation / mutation screening,R587.1
  4. Effects of Simvastatin on WT1/hDMP1 Gene Expression Profiles of Human Acute Myeloid Leukemia Cells Lines,R733.71
  5. The Study of Clinical Chracteristics and Pathogenesis of Thrombotic Thrombocytopenic Purpura,R554.6
  6. Qingdao region of hepatitis B virus the BCP gene mutation and hepatitis B virus associated with primary liver cancer,R512.62
  7. Aanalysis of Genotype and ORF3 Gene Mutation of Hepatitis E Virus in Wuhan,R512.6
  8. The Expression and Clinical Significance of CREB in Acute Myeloid Leukemia and Myelodysplastic Syndromes,R551.3
  9. Detection of Mutations of PAX9 and MSX1 Gene in Xinjiang Uyghur Patients with Non-syndrome Tooth Agenesis,R783
  10. The Analysis and Significance of JAK2 and TET2 Gene Mutation in Myeloproliferative Neoplasm,R733.3
  11. And aged patients with acute myeloid leukemia treatment summary,R733.71
  12. The Research of Impact of Proton Pump Inhibitor Omeprazole on the Antiplatelet Effects of Clopidogrel,R541.4
  13. The Expression of MN1 in Acute Myeloid Leukemia and Its Prognostic Significance in Other Known Genetic Markers,R733.7
  14. The Therapeutic Effect of Zishen Blood Capsules in the Treatment of Consolidation Chrmotherapy for Acute Myeloid Leukemia and Its Potential Mechanism,R733.7
  15. The Analysis of BRCA1 Exon 11、24 Mutations in the Patients with Early Onset Breast Cancer and Affected Relatives Live in Shandong, China,R737.9
  16. An idiopathic Brugada syndrome ECG levy molecular genetic analysis of pedigree,R541.7
  17. Research on Theapplication of Multi-gene Mutation Evolution Strategies in EDSS,F224
  18. Expression of Bovine Scrapie Prion Protein Gene PrP102-242 and PrP1-264 in COS-7 Cells,S852.659.7
  19. Hereditary cataract gene mutation and protein functional changes,R776.1
  20. To Detect the Expression of NF-kB in Acute Myeloid Leukemia by Real-time Quantitative Polymerase Chain Reaction,R733.7
  21. Classical and Molecular Cytogenetic Abnormalities of Adult Acute Myeloid Leukemia,R733.7

CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia > Acute leukemia
© 2012 www.DissertationTopic.Net  Mobile