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FLT3 Length Mutations, FLT3 Expression And Their Clinical Implications In Patients With Myeloid Leukemia

Posted on:2008-10-11Degree:MasterType:Thesis
Country:ChinaCandidate:L YangFull Text:PDF
GTID:2144360218951354Subject:Medicine
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Backgound and Objectives FLT3(Fms-like tyrosine kinase-3) is a member of the class III receptor tyrosine kinase family,and plays an important role in regulating the proliferation of the hematopoietic cells by the activation of the tyrosine residues and subsequent signal transduction with its ligand FL.Recently,most studies have indicated that FLT3 gene has a class of activation mutation: internal tandem duplication (ITD) in the juxtamembrane (JM) domain,which also can be called FLT3 length mutation,and the patients with FLT3-LM have some clinical features. Mutant FLT3 exhibit constitutive activity and autophosphorylation in the absence of FL binding, and then cause an aberrant signal transduction pathways, furthermore having an important pathological effect on the haematopoietic maliganancy process.Some of acute leukemia patients displayed both receptor and ligand suggesting a possible autocrine or paracrine stimulation. High level of FLT3 expression may play an important role in the pathogenesis of acute leukemia by strengthening the common signal transduction of Wt-FLT3. Some research group indicated high FLT3 mRNA level in acute myeloid Leukemia(AML) patients ,which had correlation with prognosis of the patients.The study was to investigate FLT3 length mutation (FLT3-LM) and FLT3 expression level in patients with AML and the clinical features of the patients with length mutations and high expression of FLT3.Method Analysis of FLT3-LM was performed on bone marrow samples from 95 patients with de novo AML ,22 patients with ALL and 10 healthy control by PCR. Flow cytometry is used to investigate FLT3 expression on MNC in 68 AML cases and 10 cases as normal control.Result 1.1 FLT3-LM were detected in 15 of 95(15.8%) AML patients, including 3/18 of M1, 4/24 of M2, 2/17 of M3, 5/25 of M5, 1/4 of M6. There were no noticeable deviation among the FAB subtypes(P>0.05). No FLT3-LM was found in 22 ALL and 10 heathy control.1.2 FLT3-LM was more prevalent in patients with normal karyotype(23.0%) and t(15;17)(16.7%). FLT3-LM was associated with a higher white cell count(P<0.05) , a higher percentage of bone marrow blast cells(P<0.05)1.3 FLT3-LM AML patients have no lower complete mission rate tendency or shorer survival time (P>0.05) comparing with FLT3-LM negative AML patients.2.1The expression level of FLT3 of MNC in AML patients(11.48±14.87) % was significantly higher than that in normal controls(1.10±0.31) % (P<0.05). The FLT3 expression level of MNC in FLT-LM negative AML patients (14.14±16.25) % was higher than that in FLT3-LM positive cases(5.86±6.85) % (P<0.05).2.2The FLT3 expression level were equally distributed among the FAB subtypes(P>0.05). There were no noticeable deviation among karyotypes in the expression of FLT3(P>0.05).2.3The patients with higher FLT3 expression level had a tendency of a lower remission(P<0.05)..Conclusion FLT3 mututions represent a common genetic abnormality in AML patients. AML patients with FLT3-LM was associated with a higher peripheral white cell count and a higher percentage of bone marrow blast cells but no lower complete remission rate tendency or shorer survival time camparing with FLT3-LM negative patients. Higher FLT3 expression level was found in AML patients and predict poor remission rate tendency. FLT3 expression level had no correlation with the quantity of the cells which expressed CD34. Above all, FLT3 aberration and expression level of FLT3 could be helpful to the diagnosis of leukemia ,prognosis prediction and target therapy.
Keywords/Search Tags:Acute myeloid leukemia, Gene ,FLT3, Internal tandem duplication, Expression
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