Disease relevance of Runx1t1

• The translocation (8;21), generating the AML1-ETO fusion protein, is one of the most frequent chromosomal abnormalities associated with acute myelogenous leukemia (AML) [1].
• Two days after intraperitoneal inoculation with 10(5) P388 leukemia cells/mouse to CDF1 male mice, etoposide at 10-80 mg/kg was administered intraperitoneally in bolus in the form of ETOP-OIL or in the aqueous solution form [2].
• Etoposide microcrystals suspended in oil (ETOP-OIL) were examined for their therapeutic effects on peritoneal carcinomatosis in mice [2].
• In every dose, the survival curve of the mice given ETOP-OIL was statistically significantly improved in spite of its small lethal toxicity, as compared with those given the identical dose of etoposide aqueous solution [2].

High impact information on Runx1t1

• AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency [1].
• To elucidate its role in oncogenesis, bone marrow (BM) cells were infected with a retroviral vector carrying AML1-ETO and transplanted into mice [1].
• ETO expression rapidly reduces after the initiation of adipogenesis, and this is essential to the normal induction of adipogenic gene expression [3].
• The putative transcriptional corepressor ETO/MTG8 has been extensively studied due to its involvement in a chromosomal translocation causing the t(8;21) form of acute myeloid leukemia [3].
• The BOP proteins expressed in CTLs and muscle contain zinc finger-like motifs with homology to those of the ETO/MTG8 proto-oncogene and several other proteins of interest [4].

Biological context of Runx1t1

• Contrary to full-length AML1-ETO, the truncated form promotes in vitro growth and does not obstruct the cell-cycle machinery [5].
• The translocation results in the fusion of two genes, AML1 (CBFA2) on chromosome 21 and ETO (MTG8) on chromosome 8 [6].
• We further showed that a region within ETO, containing domain II, mediates dimerization among family members [6].
• ETO-2 is 75% identical to murine ETO and shares very high sequence identities over four regions of the protein with ETO (domain I-III and zinc-finger) [6].
• In contrast to previous transgenic mouse models, we show that AML1-ETO directly stimulates granulopoiesis, suppresses erythropoiesis, and impairs the maturation of myeloid, B, and T lymphoid cells in vivo [1].

Anatomical context of Runx1t1

• The recent identification of another ETO-like protein, myeloid translocation gene-related protein 1, together with the data presented here, demonstrates that at least three ETO proteins exist with the potential to form dimers in the cell nucleus [6].
• Negative regulation of granulocytic differentiation in the myeloid precursor cell line 32Dcl3 by ear-2, a mammalian homolog of Drosophila seven-up, and a chimeric leukemogenic gene, AML1/ETO [7].
• The permeability characteristics of digoxin (DIG), paclitaxel (TAX) and etoposide (ETOP) were measured in ileum from mdr1a (-/-) and wild-type (FVB) mice mounted in Ussing chambers [8].
• The estimated number of P388 leukemia cells in the lymph nodes in the ETOP-CH group was statistically significantly (by Student's t-test, P less than 0.05-0.005) less than the number of P388 leukemia cells in the other treatment groups [9].

Associations of Runx1t1 with chemical compounds

• Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells [10].

Regulatory relationships of Runx1t1

• Analyses have demonstrated that AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia [5].

Other interactions of Runx1t1

• ETO-2, a new member of the ETO-family of nuclear proteins [6].

Analytical, diagnostic and therapeutic context of Runx1t1

• Gene targeting reveals a crucial role for MTG8 in the gut [11].

References