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The Analysis Of The Chromosome Karyotype Of The Patients With Acute Lymphocytic Leukemia And The Study On The MAPK Signal Pathway Of The Acute Lymphocytic Leukemia Cells

Posted on:2014-02-20Degree:MasterType:Thesis
Country:ChinaCandidate:Q Y LiFull Text:PDF
GTID:2234330398977506Subject:Internal medicine
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Part1Background and ObjectiveAcute lymphoblastic leukemia (ALL) is a malignant clonal hematopoietic system disease, ALL patients often habored abnormal chromosome karyotype, chromosome karyotype and the prognosis of the disease have a certain relationship. The world health organization (WHO) applies the chromosome analysis as an index of the diagnosis of leukemia.Materials and Methods110ALL patients were treated in our hospital and successfully were carried out the the karyotype analysis from April2008to September2012. Their bone marrow smears were carried out with Wright staining, and histochemistry staining200cells were reviewed under an optical microscope,FAB classification was made according to this.5ml bone marrow was aspirated from each patient and the cells were seeded. The chromosome were prepared with Giemsa anti-band technology.The description of the chromosomal abnormalities was according to the human cytogenetics international naming system (ISCN1995). Spss statistics17.0χ2test, P<0.05was regarded as statistical significance.ResultsAmong110patients with ALL,71of them(64.5%) had clonal chromsomal normalities,39of them(35.5%) had clonal chromsomal abnormalities,24of them(21.8%) had chromosome structural abnormalities,11of them(10%) had chromosome number abnormalities,3of them (2.7%) had chromosome number and structure abnormalities.1of them had chromosomal complex karyotype.Among42children with ALL,12of them(28.6%) had clonal chromsomal abnormalities,5of them(11.9%) with t (9;22)(q34; qll).Among68adult patients with ALL,27of them(39.7%) had clonal chromsomal abnormalities,11of them(16.2%) with t(9;22)(q34;q11). The proportion of adults patients with t (9;22)(q34;11) is not statistically significant difference from that children patients with t (9;22)(q34;11)(P>0.05). Efficacy in patients with ALL with t (9;22)(q34;11) is worse than that of the other patients. Efficacy in patients with ALL with hyperdiploidy karyotype(≥50) is not different from that of the patients with normal karyotype.No significant difference in efficacy between the adult ALL patients with t (9;22)(q34; q11) and the children ALL patients with t (9;22)(q34; q11)(p>0.05)ConclusionsChromosome karyotype of the ALL patients is random, chromosomal translocations such as t(9;22)(q34;q11) and t(4;11)(q21;q23) were frequently and the patients with these abnormalities have low CR rate.Part2Background and ObjectiveIt is reported that about5%of ALL children have bcr/abl fusion gene, and the adults ALL is20%~30%. With BCR/abl gene encoding of P190protein with tyrosine kinase activity, P190bcr/abl protein can activate the Ras/Erk signaling pathway. The inhibition of the downstream signaling Ras/Erk pathway by P190protein inhibitor can study the pathogenesis of acute lymphoblastic leukemia and to provide a basis for target therapy.Materials and MethodsSeven ALL patients treated in our hospital since September2012and four healthy people were studied, leukemia cells of peripheral blood of seven ALL patients detected by flow cytometry were more than90%.The mononuclear cells were collected and cultured.The cells were treated with PD98059.The c-jun,c-fos and TAK1mRNA expression were detected by SYBR Green Ⅱ real-time quantitative PCR.Paired samples were analysed by non-parametric Wilcoxon paired symbols rank sum test independent samples were analysed by the Mann-Whitney U test, P<0.05was regarded as statistical significance.ResultsThe expressions of c-fos mRNA(p=0.014) and TAK1mRNA(p=0.017) were significantly high in primary culture cells of ALL compared with normal people. After treated with PD98059, c-fos mRNA and c-jun mRNA expression levels decreased in all of the7patients; TAK1mRNA in5cases were down-regulated and2were up-regulated; The differences were statistically significant; the expressions of the c-fos mRNA, c-jun mRNA and TAK1mRNA were no statistical differences compared with healthy people.ConclusionsThe expression of the c-fos mRNA,c-jun mRNA,TALl mRNA were high in the mononuclear cells of the ALL patients.Blocking the Ras/Erk pathway can down-regulate the expression of the c-fos mRNA,c-jun mRNA,TALl mRNA...
Keywords/Search Tags:ALL, Karyotype, c-fos, c-jun, TAK1
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