RUNX1 And NRAS In Chinese Adult Patients With AML:the Result From A Comprehensive Genetic And Clinical Analysis

Background: Acute myeloid leukemia(AML)is a malignant clonal disease originated from myelopoietic stem/progenitor cells,recent studies have found that RUNX1 is a key regulator of hematopoiesis and is involved in hematopoietic stem cell emergence and regulation.It affects the self-renewal of hematopoietic stem cells and the differentiation of cell lineage through chromosomal translocation and somatic mutation,thus participating in the development of AML.Neuroblastoma rat sarcoma virus oncogene homology(NRAS)belongs to the RAS triphosphate GTPase gene family,studies have found that NRAS mutations are mainly involved in the development of AML by regulating cell proliferation,differentiation,and apoptosis.However,the effect of NRAS mutation prognosis of AML has not yet been determined.Objective: The aim of this study was to determine the mutation rate and the distribution of RUNX1 and NRAS genes in Chinese adult AML.To explore the relationship between RUNX1 and NRAS mutations and clinical characteristics of patients,as well as the effects of these two mutations on the survival of patients were analyzed.Methods: The genomic DNA of bone marrow was screened by polymerase chain reaction(PCR)and sequencing for RUNX1 and NRAS mutations.At the same time,the mutations of ASXL1,DNMT3 A,TET2,CEBPA,FLT3,IDH2,NPM1 and c-KIT genes were also detected to analyze the association between the two gene mutations.Results: 1.A total of 12 RUNX1 mutations were found in 108 patients with primary AML,with a mutation rate of 11.1%,including 6 cases of A166 G,4 cases of A142 T and 2 cases of A162 L.Compared with the wild group,patients in the RUNX1 mutation group were older(P< 0.01),easy to accompany with FLT3-ITD gene mutations,but mutually exclusive with CEBPA double mutations(P<0.05).The CR and OS rate are lower(P<0.01),but there was no statistically significant difference in gender,white blood cell count,hemoglobin,platelet count,lactate dehydrogenase level,bone marrow blast cell ratio,FAB typing,immunophenotyping,cytogenetics,and other gene mutations(P>0.05).2.There were 11 cases of NRAS mutation and the mutation rate was 10.2 %,including 6 cases of G12 D,3 cases of G13 D,and 2 cases of G61 K.The peripheral blood leukocyte count of patients with NRAS mutation was higher(P<0.05),which are associated with M4 subtypes and are not easily correlated with M2 subtypes(P<0.05),and it was easier to express CD13(P<0.05).However,there was no significant difference in gender,age,hemoglobin,platelet count,lactate dehydrogenase level,bone marrow blast cell ratio,cytogenetics,relationship with other gene mutations,CR rate and OS(P>0.05).3.Two patients carried NRAS and RUNX1 gene mutations at the same time,but there was no statistical significance(P>0.05).Conclusion: 1.RUNX1 gene mutations have a high incidence in the first diagnosis of AML in old age,and are prone to the occurrence of FLT-3 gene mutations.Patients with RUNX1 gene mutations have a poor prognosis,and the test is conducive to guiding the treatment and prognosis assessment of AML patients.2.Peripheral blood leukocyte count was higher in newly diagnosed AML patients with NRAS gene mutation,which are associated with M4 subtypes and are not easily correlated with M2 subtypes.However,no adverse effects of NRAS gene mutation on CR and OS were found in this study.