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Objective:To investigate the FLT3-ITD and NPM1 gene mutation rate in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with normal karyotype,as well as the different mutation rate in their subtypes,Meanwhile,the clinical features and complete remission rate were observed in primary acute myeloid leukemia patients with the two kinds of mutations.Methods:A retrospective analysis from January 2008 to October 2010, Hebei Province People’s Hospital of untreated 201 cases of AML and MDS patients clinical data,including untreated newly diagnosed AML125 (include t(15,17) and t(8,21) M3 and M2 patients)(male 64 cases,female 61 cases),MDS 76 patients (42 males and 34 females). Extraction of the bone marrow mononuclear cells in patients with DNA,using genomic DNA-PCR and DNA direct sequence to detect all patients with FLT3 exon 14-15 in the ITD and NPM1 gene mutation in exon 12.Detection of fusion genes,including PML/RARa and AML1-ETO.Results:1 125 patients with normal karyotype in untreated newly diagnosed acute myeloid leukemia patients,NPM1 gene mutations 57 cases,the number of cases were: M1 2 cases (28.6%),M2 12 cases (38.7%),M4 12 cases (60%),M5a 14 cases (66.7%),M5b 17 cases (73.9%),M3 20 cases,M4E_O 3 cases no NPM1 gene mutation in the expression,NPM1 gene mutations in 125 cases untreated of normal karyotype acute myeloid leukemia the total expression was 45.6%; FLT3-ITD mutation 50 casess,the number of cases were: M1 1 case (14.3%),M2 6 cases (19.4%),M3 16 cases (80%) M4 8 cases (40%),M5a 9 cases (42.9%),M5b 10cases (43.5%),M4E_O in FLT3-ITD mutation was no expression,FLT3-ITD mutations in 125 patients with untreated acute myeloid leukemia normal karyotype the total cellular expression was 40%;125 patients in the NPM1~+/FLT3-ITD~-total 23 cases (18.4%) , NPM1~-/FLT3-ITD~- accounted for 39 cases (31.2%) ,NPM1~+/FLT3-ITD~+ accounted for 45 cases (36.0%),NPM1~-/FLT3-ITD~+ accounted for 18 cases (14.4%);there were 85 cases of AML patients after one course of chemotherapy reached CR,CR rate 68%,the other 40 patients underwent a course of less than complete remission after chemotherapy (CR),no reach complete remission 45cases , 8 cases were tested NPM1~+/FLT3-ITD~+,15 cases NPM1~-/FLT3-ITD~-,17 cases NPM1~-/FLT3-ITD~+ patients to continue after 2 cycles of chemotherapy,including 29 cases of CR,more than 11 cases did not reach CR,the 11 cases NPM1~-/FLT3-ITD~+ patients;after the second course of chemotherapy CR rate 91.2%;23cases NPM1~+/FLT3-ITD~-patients after treatment reached CR,the time of reached CR was 15±5 days,39 cases NPM1~-/FLT3-ITD~- reached CR time was 21±10 days,45 patients with NPM1 +/FLT3-ITD~+ reached CR time was 23±9 days,7 patients with NPM1~-/FLT3-ITD~+ reached CR time was 40±18 days; 57 patients with NPM1 mutation positive female patients accounted for 34 cases (59.6%),males accounted for 23 cases (40.4%),and are expressed as percentage of bone marrow blast cells,peripheral blood leukocyte and higher platelet count,none of pancytopenia,bone marrow nucleated cell proliferation is usually significantly active; 50 patients with FLT3-ITD mutation positive female patients accounted for 27 cases (54.0%),males accounted for 23 cases (46.0%),general expressed as percentage of bone marrow blast cells,peripheral white blood cells high,including 3 cases of pancytopenia,bone marrow nucleated cell proliferation generally was active.2 76 cases of MDS patients,there were a lot of changes in different chromosomes,include 7 cases del(5q),15 cases +7,13 cases del(8),10 cases del(20q),8 cases normal karyotype patients,the othe 23 cases complex karyotype;NPM1 gene mutation involved on chromosome 5,the NPM1 mutation is: RARS 1 case (1.3%), RAEB-1 5 cases (6.6%), RAEB-2 1 case (1.3%),other subtypes were no expression of NPM1 gene mutations, NPM1 mutations in the expression of the total MDS was 9.2%; FLT3-ITD mutation expression as: RAEB-1 2 cases (2.6%),RAEB-2 4 cases (5.3%),other subtypes,FLT3-ITD mutation was no expression,FLT3-ITD mutation expression in MDS was 7.9% overall;of which 5 cases RAEB-1 for the NPM1~+/FLT3-ITD~- , 2 cases RAEB-1 and 1 case RAEB-2 for the NPM1~+/FLT3-ITD~+,4 cases RAEB-2 is NPM1~-/FLT3-ITD~+,15 cases RAEB-1 and 18 cases RAEB-2 for the NPM1~-/FLT3-ITD~-; NPM1~+/FLT3-ITD~+ in 1 case RAEB-1 and 1 case RAEB-2 at 1 month were converted to AML.3 10 cases of immune thrombocytopenia,10 cases of aplastic anemia,10 patients with multiple myeloma,10 cases of non Hodgkin lymphoma,10 cases of acute lymphoblastic leukemia,10 cases of megaloblastic anemia were not expression in detect FLT3-ITD and NPM1 mutation.4 16 cases FLT3-ITD mutation positive of the M3 was detected in patients with PML/RARa expression,FLT3-ITD mutation in 6 cases of M2 positive patients include five cases detected ETO expression; and 57 cases of NPM1 mutation positive patients was not detected specific fusion gene expression.Conclusion:1 The mutation rates of NPM1 were different in the subtypes of untreated AML. It was M1 <M2 <M4 <M5a <M5b,There is no significant differences between the subtypes. FLT3-ITD mutation rates in untreated AML heterogeneity of the subtypes,it appears in all subtypes except M4E_O outside,the other low to high mutation rate was M1 <M2 <M4 < M5a <M5b <M3,but the M3 group of FLT3-ITD mutation was higher than in other types of group.2 In MDS subtypes,NPM1 mutation more common expression in RAEB-1,FLT3-ITD mutation more common expression in RAEB-2.3 NPM1 mutation and FLT3-ITD mutation were more common in female,the proportion of bone marrow blast cells,peripheral blood leukocyte and platelet counts were higher.4 NPM1~+/FLT3-ITD~-group response time of the shortest,the highest response rate,NPM1~-/FLT3-ITD~+group remission longer,the lowest response rate.
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