ABSTRACT
Objective:To investigate the molecular genetic and clinical characteristics of MEF2D-BCL9 fusion gene-positive acute B-cell lymphoblastic leukemia (B-ALL), and to provide the reference for the diagnosis and treatment of the disease.Methods:The medical record and experimental examination data of a 18-year-old female MEF2D-BCL9 fusion gene-positive B-ALL patient were retrospectively analyzed. The clinical manifestations and biological characteristics of MEF2D-BCL9 fusion gene-positive B-ALL were summarized.Results:This 18-year-old female patient was treated in a local hospital in December 2018 and was diagnosed as B-ALL. She achieved complete remission after chemotherapy and recurred at 6 months after the initial onset, and then she was admitted to Hebei Yanda Ludaopei Hospital in the 9 months after the initial onset.MEF2D-BCL9 fusion gene was detected through RNA-sequencing (RNA-seq) and verified by using polymerase chain reaction and Sanger sequencing. Bone marrow cell morphology was similar to mature B cells with vacuoles but without characteristic chromosome karyotype abnormalities. The patient achieved remission after VLD regimen chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy and bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). She has maintained complete remission for 2 years at the last follow-up in February 2022.Conclusions:MEF2D-BCL9 fusion gene-positive B-ALL is characterized with high risk, early relapse and poor prognosis. These patients may benefit from CAR-T and allo-HSCT. It further emphasizes the importance of taking MEF2D-BCL9 fusion gene into the detection or identification by using RNA-seq, particularly for those newly diagnosed B-ALL patients in children and adolescents with specific bone marrow morphology.
ABSTRACT
[Objective]To investigate the role and the potential target of miR-92b-3p in angiotensin Ⅱ(Ang-Ⅱ)-induced mouse cardiac hypertrophy.[Methods]Ang-Ⅱ-induced cardiac hypertrophy models were established in adult C57BL/6 mice. AgomiR-92b-3p,the cholesterol-modified miR-92b-3p mimic,was delivered to increase the level of miR-92b-3p in mouse myocar?dium via tail vein injection. In the present study,three groups of mice were used in the animal experiment as follows,the agomiR-negative control(agomiR-NC)+saline group,the agomiR-NC+Ang-Ⅱgroup and the agomiR-92b-3p+Ang-Ⅱgroup. A cell model of cardiac hypertrophy was also established in Ang-Ⅱ-induced neonatal mouse cardiomyocytes in this study Luciferase activity was assayed after transfection using a luciferase reporter assay system. The expression of Myocyte-specific enhancer factor 2D( MEF2D) and hypertrophy-related genes atrial natriuretic peptide (ANP),cardiac muscle α-actin (ACTA1) and β-myosin heavy chain (MHC)at mRNA and protein levels in Ang-Ⅱ-induced hypertrophic myocardium and cardiomyocytes were detected by qRT-PCR and Western blot,respectively.[Results]The expression of ANP,ACTA1,β-MHC were markedly increased in Ang-Ⅱ-induced hypertrophic myocardium and cardiomyocytes. Dual luciferase reporter assay revealed that MEF2D is a potential target gene of miR-92b-3p. And miR-92b-3p can reduce the expression of MEF2D at the post-transcriptional level. Functionally,miR-92b-3p mimic, consistent with MEF2D siRNA,inhibited cell size increase and protein expression of ANP,ACTA1 andβ-MHC in Ang-II-treated mouse cardiomyocytes.[Conclusions]MEF2D is a novel target of miR-92b-3p,a target gene of miR-92b-3,which mediates the ef?fect of miR-92b-3p on attenuating cardiomyocyte hypertrophy.