1.A Novel Translocation(1;9)(p22;q34) Resulting In DEK/NUP214 In One Patient With Acute Myeloid Leukemia: A Case Report And Literature Review 2.Expression And Prognosis Of IGF2BPs And Nek2 In AML

Abstract:We report a 46-year-old female patient with acute myeloid leukemia (AML)-M4,accompanying by a consistent chromosomal abnormality, t(1;9)-(p22;q34).The examination of the transcriptome resequencing, PCR and FISH verified that this translocation can form the known fusion gene DKE/NUP214,which results from t(6;9)(p23;q34) in the previous reports. To our knowledge, it is the first report about this variant translocation and brings the new insight of AML with DEK/NUP214.Insulin-like growth factor 2 mRNA-binding proteins are a conserved family of RNA-binding, oncofetal proteins, which are mainly expressed during embryogenesis..IGF2BP1,IGF2BP2,IGF2BF3,the members of IGF2 BPs,act in various important aspects of cell function,such as cell polarization,migration,morphology, metabolism,proliferation and differentiation. Now, researchers believe they are highly associated with cancer metastasis and the expression of oncogenic factors(KRAS,MYC and MDR1).NEK2, a member of the serine/threonine kinase family, has been implicated in regulation of centrosome separation and spindle formation. In vivo, overexpression of NEK2 cat! induce chromosomal instability and aneuploidy. It suggests that Nek2 is associated with drug resistance in cancer, and has an influence on clinical outcome. The conclusion has been proved in many tumors,such as breast cancer, non-small cell lung cancer, multiple myeloma.Objective: To investigate the role of Ang-1, IGF2BP2、IGF2BP3、Nek2 in acute myeloid lexikemia and the relationship between these genes and prognosis.Methods:1.Collecting the bone marrow samples of the newly diagnosed AML from the leukemia wards. Blood Diseases Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College(CAMS & PUMC). All patients gave their informed consent to participate in the study.2.mRNA was extracted the ftom the mono打uclear cells(BMMNCs) of the bone marrow samples, and reverse transcripted into cDNA.3.Expression of IGF2BP2、IGF2BP3、Nek2 in BMCs were detected by RQ-PCR.4.Relationships between IGF2BP2、IGF2BP3、Nek2 and the patients’ clinical data were analyzed.Results:1.IGF2BP2、IGF2BP3、Nek2 were expressed in several cell lines,including K562、NB4、U937、HL60、Jurkat、Kasumi、THPl、Skno-1.2.There are so significant difference between male and female on the expression level of IGF2BP2、IGF2BP3、Nek2.3.There are no significant difference between WBC at diagnosis and the expreission level of IGF2BP2、IGF2BP3、Nek2.4.No defference of the 3 genes’expression level was found between the samples diagnosed M4、M5,M1、M2a、M6andM2b、M3.5.139 patients in all had been evaluated,which involved 121 patients with CR and 18 patients without CR. The differences of three genes’ expression between the group of CR and non-CR were not significant i打 statistics.6.Level of IGF2BP2 in patients with poor-risk was higher than that with better-risk(better-risk group vs poor-risk group,p=0.004). Level of IGF2BP2 in patients with intermediate-risk was higher than that with better-risk, but their differences were not significant in statistics(P=0.087). The same phenomenon did not emerge in the study the other two genes. Levels of the three genes in patients with MLL+、FLT3/ITD+、NPM1+、CEBPA++、C-kit+ was not different from that with MLL+、FLT3/ITD-、NPM1-、CEBPA-、C-kit-.7.There is no relation between the expression level of the three genes and the accumulation of unfavorable prognosis factors.8.IGF2BP2 and IGF2BP2 had a weak positive correlation(r=0.369,p<0.001).IGF2BP2 and Nek2 had a weak positive correlation(r=0.387,p<0.001). IGF2巧P3 and Nek2 had a weak positive correlation(r=0.314,P<0.001). In IGF2 BPS family,the expression level of IGF2BP2 is higher than that of IGF2BP3, and there is an significant difference in statistics.9.We defined the whole patients to two groups by the median gene expression level,respectively. We found overexpression of three genes have no influence on overall survival and relapse free survival.The OS and RFS of patient with overexpression of IGF2BP2 is similar to that of patient with unoverexpression of IGF2BP2(p=0.736,p=0.468).It is the same as to the other two genes.There are no significant difference between the CR rate of tile three group with lower gene expression level and that with higher genes level.Conclusion:The three genes are expressed of different level in AML,but we have not seen that they are significantly related to clinical outcome.