Short hairpin RNA knockdown of Ets1 in MLL/EB1 cells reduced the expression of CD115, apoptosis rate, competitive engraftment to BM and spleen, and incidence of leukemia and prolonged the survival of the diseased mice.
Approach and Results- We screened various combinations of transcription factors, including Myocd (myocardin), Mef2C (myocyte enhancer factor 2C), Mef2B (myocyte enhancer factor 2B), Mkl1 (MKL [megakaryoblastic leukemia]/Myocd-like 1), Gata4 (GATA-binding protein 4), Gata5 (GATA-binding protein 5), Gata6 (GATA-binding protein 6), Ets1 (E26 avian leukemia oncogene 1, 5' domain), and their corresponding carboxyterminal fusions to the transactivation domain of MyoD (myogenic differentiation 1)-indicated by *-for their effects on reprogramming mouse embryonic fibroblasts and human adult dermal fibroblasts to the smooth muscle cell fate as determined by the expression of specific markers.
Binding of a Smad4/Ets-1 complex to a novel intragenic regulatory element in exon12 of FPGS underlies decreased gene expression and antifolate resistance in leukemia.
The role of two members of the ETS (E26 avian leukemia oncogene) family of transcription factors, ETS-1 and ETS-2, has been investigated in many cancers but has not yet been studied in ocular tumors.
The ERGB gene, like human ETS1, is located on chromosome 11 and is transposed to chromosome 4 as a result of the translocation t(4;11) associated with leukemia.
The absence of ets-1 amplification in t(11;19) and its presence in the t(4,11) and t(9;11) translocations demonstrated by others suggests the possible existence of different molecular mechanisms involving the ets-1 oncogene in the pathogenesis of these leukemias.
Although ETS1 was moved to the derivative chromosome 19 as a result of the t(11;19), we conclude that this oncogene is not close to the chromosome 11 breakpoint and is unlikely to be involved in this leukaemia.
Our data showed no evidence of direct involvement of these genes in this leukemia but enabled a partial genetic map of this important region of the human genome to be constructed: 11cen--NCAM--CD3([G, D], E)--parallel--(ETS1, THY1)--11qter.
These findings indicate that a chromosome region (11q24----qter), including the Hu-ets-1 gene, of the ML cells is deleted as a result of the primary cytogenetic change and that heterogeneity is present in the mechanism of human leukemia involving the 11q23----q24 region.
The human ets-1 gene was found to translocate from chromosome 11 to 4 in the t(4;11)(q21;23), a translocation characteristic of a subtype of leukemia that represents the expansion of a myeloid/lymphoid precursor cell.