Expression And Significance Of Autocrine Motility Factor Receptor In Childhood Acute Myelogenous Leukemia

BackgroundAcute leukemia ranks first place in our children’s malignant diseases, and thechildhood acute myeloid leukemia accounts for about20%of acute leukemia. Acutemyeloid leukemia is a group of heterogeneous malignant tumors, and there weresignificant differences in clinical efficacy and prognosis of various types of AML.The remission rate the rest of types was only about75%in addition to acutepromyelocytic leukemia,5-year-disease-free survival rate by about50%. In recentyears, with the development of life science, the pathogenesis of leukemia and relatedtreatment are deeply studied, and some indicators which can be used to judge thedisease type, risk classification and prognosis of the leukemia are found. Discoveryand research on these indicators has become a hotspot in recent years.Autocrine motility factor receptor(AMFR) as a tumor-associated protein hasaroused widespread concern. In many human tumors, such as lung cancer, breastcancer, esophageal cancer, stomach cancer, colon cancer, colorectal cancer, livercancer and skin cancer, the AMFR is highly expressed and significantly correlatedwith clinical stage of the tumor. The survival rate and survival time with highexpression of AMFR was significantly decreased, which can prove AMFR may be asan independent predictor in the poor prognosis of neoplastic diseases.While AMFR was less researched in hematologic malignancies, Sofia Grund andother scholars’studies have found that the expression levels of AMFR is significantlyincreased in peripheral blood single cell surface of patients with chronic lymphocytic leukemia (CLL). So AMFR may be one of the independent molecular markers of poorprognosis. Whether AMFR have a high expression and can judge prognosis ofleukemia in children with acute leukemia has not been reported.Objective：Explore the significance of autocrine motility factor receptor in childhood acutemyelogenous leukemia occurrence, development and the clinical prognostic bytesting the expression level of autocrine motility factor receptor.Methods：Form December2011to December2013,63cases children with acutemyelogenous leukemia（except acute promyelocytic leukemia）in the First AffiliatedHospital of Zhengzhou University pediatric were enrolled in this research，including34males and29females, the median age of which is5.5years (0.5-12years old).The63cases include35children newly diagnosed（the initial group），18ones withcomplete remission（the complete remission group）and10cases suffered from therecurrence of acute myelogenous leukemia（the recurrence group）.While50childrenwere enrolled （the control group）at the same time which had been ruled out themalignant diseases，including29males and21females, the median age of which is4.5years (1.0-13years old).The Follow-up time is to the end of December31,2013,and lost visitor’s follow-up time is the date of lost to the follow-up.①Detect the autocrine motility factor receptor gene Messenger RNA(mRNA)and protein expression lever of the bone marrow mononuclear cells in acutemyelogenous leukemia children and not suffering from cancer Children,by using thetecnology of Reverse transcription-polymerase chain reaction and western-bloting.②According to AMFR gene mRNA expression level of the binary bit tangentpoint,divide the initial group into two groups of the AMFR-mRNA high expressionand AMFR-mRNA low expression group. Analysis the2years overall survival timewith the Kaplan Meier method. Analysis the relationship of the AMFR expressionlevel, age, gender, number of peripheral white blood counts and the proportion of bone marrow blast cells factors with the prognosis of children in the initial group withCox regression model of single factor and multiple factors.Results：①Compared with the control group,the children with AML has a higherexpression lever of AMFR gene mRNA. The recurrence group has a higher lever thanthe initial group and he complete remission group,respectively；the initial group ishigher than the complete remission group,and the complete remission group has ahigher lever than the control group,comparisons between these groups havestatistically significant (P <0.05).And compared with the control group, the childrenwith AML has a higher expression lever of AMFR Protein expression lever. Therecurrence group has a higher lever than and ease group,respectively;the initial groupis higher than the complete remission group,and the complete remission group has ahigher lever than the control group,comparisons between these groups havestatistically significant (P <0.05).②The prognosis of the AMFR-mRNA high expression group is poor than theAMFR-mRNA low expression group,by the Kaplan Meier analysis method. themedian survival period of AMFR high expression group and low expression group ofis710days respectively (95%CI:116.409-245.251) and69days (95%CI:14.424-123.576), respectively. And there is statistical significances in the overall survival(OS)analysis between these two groups with the method of Log-Rank statisticsanalysis,x2=15.942，P <0.001.③Use Cox regression model to correct and analyse the factor of gender, age,peripheral blood leukocyte counts and the proportion of bone marrow primitive cellsand the FAB type of leukemia, AMFR gene mRNA expression level is a factoreffecting the poor prognosis of AML, AMFR regression coefficients is1.221and HRis2.556.Conclusion①Acute myelogenous leukemia has a high expression lever ofAMFR; ②The high expression lever of AMFR may be a factor of the poor prognosisof children with acute myelogenous leukemia;③Expression level of AMFR gene would be used as a clinical prognosis andrisk stratification indicator of acute myelogenous leukemia.