Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The EEN (extra eleven nineteen) gene, located on chromosome 19p13, was cloned as a fusion with MLL from a patient with acute myeloid leukemia (AML) with translocation t(11;19)(q23;p13). In this study, we characterized the genomic structure of the EEN gene, including its 5' regulatory region and transcription start site (TSS). We found that Sp1 could bind to the guanine-cytosine (GC)-stretch of the EEN promoter and was critical for the normal EEN expression, whereas the leukemia-associated fusion protein AML1-ETO could aberrantly transactivate the EEN gene through an AML1 binding site. Of note, overexpressed EEN showed oncogenic properties, such as transforming potential in NIH3T3 cells, stimulating cell proliferation, and increasing the activity of transcriptional factor AP-1. Retroviral transduction of EEN increased self-renewal and proliferation of murine hematopoietic progenitor cells. Moreover, Kasumi-1 and HL60-cell growth was inhibited with down-regulation of EEN by RNAi. These findings demonstrate that EEN might be a common target in 2 major types of AML associated with MLL or AML1 translocations, and overexpression of EEN may play an essential role in leukemogenesis.
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PMID:Aberrant transcriptional regulation of the MLL fusion partner EEN by AML1-ETO and its implication in leukemogenesis. 1699 Jun 10

The EEN (extra eleven nineteen) gene is one of the fusion partners of mixed-lineage leukemia, located on chromosome 19p13. Here we cloned two een genes (designated as eena and eenb) in zebrafish, which are assigned to linkage groups 8 and 2, respectively. Whole-mount in situ hybridization assay showed that eena and eenb have overlapping but distinct expression patterns during embryogenesis. Ubiquitous or targeted overexpression of eena, but not eenb, into wild-type or transgenic embryos (green fluorescent protein-labeled myeloid progenitors) induced a significant proliferation and ectopic distribution of myeloid progenitors in the yolk sac. Using a morpholino antisense gene knockdown approach, we showed that the number of myeloid progenitors and their downstream mature myelomonocytic cells was significantly decreased in the eena- deficient embryos. Mechanistically, overexpression of eena selectively stimulated ERK phosphorylation and increased the level of transcription factor c-Fos in vitro and in vivo, whereas eena lacking the Src homology 3 domain completely abolished these effects. Furthermore, a MAPK/ERK kinase (MEK) inhibitor, PD98059, blocked the eena-induced cell proliferation and activation of ERK signaling. The results suggest that eena plays an important role in the development of the myeloid cell through activation of the ERK pathway and may provide a valuable reference for future studies of the role of EEN in leukemogenesis.
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PMID:eena Promotes myeloid proliferation through stimulating ERK1/2 phosphorylation in zebrafish. 1841 15

As a result of recurrent chromosomal translocations in acute leukemias, the mixed-lineage-leukemia (MLL) gene fuses with a variety of partner genes, which include several members of the septin gene family. SEPT9 is a very rare but recurrent fusion partner of MLL, and has recently been implicated in the oncogenesis of various malignancies. Herein, we report a case of de novo acute monocytic leukemia (M5b) with t(11;17)(q23;q25). MLL involvement was revealed by fluorescent in situ hybridization (FISH) analysis, and an MLL/SEP9 fusion transcript was detected by RT-PCR. Sequencing analysis further showed that, in contrast to originally reported cases, MLL exon 8 was fused not with SEPT9 exon 3 but with exon 2, which codes for the unique N-terminal region of the SEPT9_v1 isoform, the region implicated in the regulation of gene expression and cell proliferation. We did not detect any mutation of FLT3, which was expressed at a relatively low level in the leukemic cells. Relapsing after a very short complete remission, the leukemia progressed rapidly and became fatal in spite of intensive therapies including hematopoietic stem cell transplantation. It is thus suggested that, in common with the original MLL/SEPT9 cases, monocytic differentiation and a poor prognosis may also be associated with acute myeloid leukemia with the variant MLL/SEPT9 fusion transcript.
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PMID:A variant-type MLL/SEPT9 fusion transcript in adult de novo acute monocytic leukemia (M5b) with t(11;17)(q23;q25). 1864 54


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