Clinical Characteristics And Early Treatment Response Of Children With Acute Lymphoblastic Leukemia Modified By Fusion Gene And RAS Gene

ObjectiveAcute lymphoblastic leukemia is a kind of common hematologic malignancy disease in children.With the clinical application of cytogenetics and molecular biology technology,great progress has been made in the diagnosis and treatment of children with acute lymphoblastic leukemia,which has improved the clinical cure rate.However,some children with acute lymphoblastic leukemia are still refractory or relapse after remission.Therefore,it is very important to explore the factors influencing the prognosis of children with acute lymphoblastic leukemia for the formulation of individualized treatment and improvement of the prognosis of children.This study analyzed the relevant clinical features and early therapeutic responses of children with acute lymphoblastic leukemia with RAS gene and fusion gene alteration,in order to provide clinical reference for the formulation of individualized diagnosis and treatment and prognosis of children with acute lymphoblastic leukemia.MethodsClinical data of 111 children with initially treated acute lymphoblastic leukemia who met the inclusion criteria were collected from the Department of Pediatrics,The First Affiliated Hospital of Guangzhou Medical University from July 2017 to September 2022.Bone marrow morphology,immune typing,chromosome karyotype,RAS gene and fusion gene were detected in all the children,and clinical characteristics and early treatment response were analyzed.Results1.Fusion gene test results of 111 newly diagnosed ALL children showed that 60cases(54.1%)had negative fusion gene and 51 cases(45.9%)had positive fusion gene.A total of 6 fusion gene positive types were detected.According to the proportion of each fusion gene positive children in the overall order from high to low: TEL/AML1 positive in 18 cases(16.2%),TCF3/PBX1 positive in 11 cases(9.9%),HOX11 positive in 6 cases(5.4%),MLL rearrangement in 6 cases(5.4%),BCR/ABL positive in 5 cases(4.5%)and SI 5 cases(4.5%)were positive for L/TAL1,and all fusion gene types were detected independently,and no two or more fusion gene types were detected simultaneously.RAS gene examination results of 111 children with ALL showed that 80 children(72.1%)had no mutation,31 children(27.9%)had mutation,including 13 children(11.7%)with N-RAS mutation and 18 children(16.2%)with K-RAS mutation.No gene type combining N-RAS mutation,K-RAS mutation and H-RAS gene type was detected.2.Comparison of clinical characteristics between fusion gene negative and positive ALL children: there were no significant differences in gender composition,extramedullary leukemia and immune typing(P > 0.05),but there were significant differences in age composition,white blood cell count,risk typing and chromosome karyotype(P < 0.05).Comparison of early treatment response: there were statistically significant differences in prednisone response between fusion gene negative and fusion gene positive ALL children(P < 0.05),but there were no statistically significant differences in bone marrow remission at day 33 of induction therapy,MRD level at day19 and MRD level at day 33 of induction therapy(P > 0.05).3.Comparison of clinical characteristics between fusion gene negative group and each fusion gene positive group: there were statistical differences in age composition,leukocyte count,extramedullary leukemia,immune typing and risk typing(P < 0.05),but there were no statistical differences in gender composition and chromosome karyotype(P > 0.05).Comparison of early treatment response: there were statistical differences in prednisone response,MRD level in bone marrow at day 19 of induction therapy,and MRD level in bone marrow at day 33 of induction therapy between fusion gene negative group and fusion gene positive group(P < 0.05),but there was no statistical difference in remission at day 33 of induction therapy(P > 0.05).4.Comparison of clinical characteristics of RAS mutation and non-mutation children:there were statistically significant differences in risk classification(P < 0.05),but no statistically significant differences in gender,age,extramedullary leukemia,leukocyte count,immune classification and chromosome karyotype(P > 0.05).Comparison of early treatment response: there were no significant differences in prednisone response,bone marrow remission at day 33,bone marrow MRD at day 19,and bone marrow MRD level at day 33 between children with RAS gene mutation and those without RAS gene mutation(P > 0.05).Conclusions1.The incidence of fusion gene and RAS gene changes was high in ALL children.Among the fusion genes,TEL/AML1 and TCF3/PBX1 were common.2.The clinical features and early reactions of ALL patients with different fusion gene positive are different.The TEL/AML1,TCF3/PBX1 genotypes responded well to early treatment,while the MLL rearrangement,HOX11,BCR/ABL1,SIL/TAL1 genotypes responded poorly to early treatment.3.The clinical features and early treatment response of ALL children with RAS gene mutation are similar to those of unmutated ALL children.