EVI1 (ecotropic viral integration site 1) is one of the most aggressive oncogenes associated with myeloid leukemia. We investigated DNA copy number aberrations in human hepatocellular carcinoma (HCC) cell lines using a high-density oligonucleotide microarray. We found that a novel amplification at the chromosomal region 3q26 occurs in the HCC cell line JHH-1, and that MECOM (MDS1 and EVI1 complex locus), which lies within the 3q26 region, was amplified. Quantitative PCR analysis of the three transcripts transcribed from MECOM indicated that only EVI1, but not the fusion transcript MDS1-EVI1 or MDS1, was overexpressed in JHH-1 cells and was significantly upregulated in 22 (61%) of 36 primary HCC tumors when compared with their non-tumorous counterparts. A copy number gain of EVI1 was observed in 24 (36%) of 66 primary HCC tumors. High EVI1 expression was significantly associated with larger tumor size and higher level of des-γ-carboxy prothrombin, a tumor marker for HCC. Knockdown of EVI1 resulted in increased induction of the cyclin-dependent kinase inhibitor p15(INK) (4B) by transforming growth factor (TGF)-β and decreased expression of c-Myc, cyclin D1, and phosphorylated Rb in TGF-β-treated cells. Consequently, knockdown of EVI1 led to reduced DNA synthesis and cell viability. Collectively, our results suggest that EVI1 is a probable target gene that acts as a driving force for the amplification at 3q26 in HCC and that the oncoprotein EVI1 antagonizes TGF-β-mediated growth inhibition of HCC cells.
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http://dx.doi.org/10.1111/cas.12694 | DOI Listing |
J Clin Invest
December 2024
Department of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, Florida, USA.
Ecotropic viral integration site 1 (EVI1/MECOM) is frequently upregulated in myeloid malignancies. Here, we present an Evi1-transgenic mouse model with inducible expression in hematopoietic stem/progenitor cells (HSPCs). Upon induction of Evi1 expression, mice displayed anemia, thrombocytopenia, lymphopenia, and erythroid and megakaryocyte dysplasia with a significant expansion of committed myeloid progenitor cells, resembling human myelodysplastic syndrome/myeloproliferative neoplasm-like (MDS/MPN-like) disease.
View Article and Find Full Text PDFBMC Pediatr
December 2024
Department of Hematology, Children's Medical Institute of Hematology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430016, China.
Objective: To investigate the clinical significance of dynamic monitoring ecotropic virus integration site-1 (EVI1) expression in childhood acute myeloid leukemia (AML).
Methods: A retrospective analysis was conducted on 113 pediatric AML patients of Wuhan Children's Hospital from 2014 to 2022. The correlation between EVI1 expression levels and clinical indicators including clinical characteristics, first complete remission (CR1), relapse, and overall survival (OS) was analyzed.
Br J Haematol
November 2024
Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg Medical Center, Faculty of Medicine, Freiburg, Germany.
Diabetes insipidus (DI) in patients with acute myeloid leukaemia (AML) and chromosome 3q alterations (EVI1/PRDM3/MECOM overexpression) constitutes a poorly understood paraneoplasia. A 44-year-old patient presented with clinical and morphological features of this syndrome but, surprisingly, disclosed the rare translocation t(1;2)(p36;p21), with massive PRDM16 overexpression. WGS and RNA sequencing suggest enhancer hijacking of the ZFP36L2 enhancer region as underlying mechanism.
View Article and Find Full Text PDFDiscov Oncol
November 2024
Department of Urology, Urology and Nephrology Center, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 158 Shangtang Road, Hangzhou, 310014, Zhejiang, China.
J Ovarian Res
October 2024
Department of Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, PR China.
The MECOM locus is a gene frequently amplified in high-grade serous ovarian carcinoma (HGSOC). Nevertheless, the body of research examining the associations among MECOM transcripts, patient prognosis, and their role in modulating the tumor immune microenvironment (TIME) remains sparse, particularly in large cohorts. This study assessed the expression of MECOM transcripts in 352 HGSOC patients and 88 normal ovarian tissues from the combined GTEx/TCGA database.
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