Disease relevance of Runx1

• In vitro colony formation of transplantable rat leukemias in comparison with human acute myeloid leukemia [1].
• In vitro colony formation in two different soft agar systems was studied with bone marrow from untreated patients suffering from acute myeloid leukemia (AML) and from rats in various stages of two different transplantable myeloid leukemias [1].
• LRP has been shown to be a strong predictor of poor response to chemotherapy and prognosis in acute myeloid leukemia and in ovarian carcinoma patients [2].
• For example, low rates of LRP positivity were seen in testicular cancer, neuroblastoma, and acute myeloid leukemia; intermediate in ovarian cancer; and high in colon, renal, and pancreatic carcinomas [2].
• The ability of nitrous oxide to inhibit the in vivo growth of hematological neoplasms was investigated in a rat model for acute myeloid leukemia (BNML) [3].

High impact information on Runx1

• Smad-Runx complexes are associated in situ with the nuclear matrix, and this association requires the intranuclear targeting signal of Runx factors [4].
• Thus, Runx-mediated intranuclear targeting of Smads is critical for the integration of two distinct pathways essential for fetal development [4].
• Development of resistance to cytarabine (AraC) is a major problem in the treatment of patients with acute myeloid leukemia (AML) [5].
• Deletion of exons 3 to 6 was also identified in 6 of 12 PHA T cells generated from the patients with resistant AML [6].
• In this study, we utilized retroviral transfer of cDNA libraries in order to identify oncogenes that are expressed in acute myeloid leukemia (AML) [7].

Biological context of Runx1

• These results are consistent with the idea that AML1 may have a role in regulating gene expression in skeletal muscle [8].
• Exposure to prostaglandin E(2) increased Runx-dependent gene transactivation independently of Runx2 binding to DNA [9].
• C/EBPdelta gene promoter activity was reduced by mutating the Runx binding sequence or by co-transfecting with Runx2 antisense expression plasmid, and was enhanced by overexpression of Runx-2 [9].
• FAST and Runx (CBFa) transcription factors, which are expressed during specific phases of embryogenesis and tissue patterning, bind directly to Smad proteins and integrate effects induced by various TGF-beta gene family members [10].
• These data suggest that MLL duplications are not implicated in the malignant transformation in AML, or alternatively, that only a few cells will acquire additional oncogenic mutations necessary to establish the malignant phenotype of AML [11].

Anatomical context of Runx1

• AML1 is expressed in skeletal muscle and is regulated by innervation [8].
• We transfected C2 muscle cells with an expression vector encoding AML1, tagged with an epitope from hemagglutinin, and we show that AML1 is a nuclear protein in muscle [8].
• Finally, estrogen increases gene transcription by the transforming growth factor-beta type I receptor gene promoter, which contains several Runx binding sequences, and enhances Smad dependent gene expression by transforming growth factor-beta in osteoblasts [12].
• It was found on the cell surface of acute myeloid leukemia (AML) blasts and cell lines derived from nonhematopoietic tissues [13].
• In both the thin-agar-layer system, which uses a feeder layer of fetal fibroblasts, and the Robinson culture system, human AML marrow failed to produce colonies [1].

Associations of Runx1 with chemical compounds

• Development and characterization of a cyclophosphamide-resistant subline of acute myeloid leukemia in the Lewis x Brown Norway hybrid rat [14].
• After 18 and subsequent passages, CY-treated AML cells remained viable despite ex vivo incubation with 70 to 100 mumol/L 4-hydroperoxycyclophosphamide (4HC) or in vivo exposure to 100 to 300 mg/kg of CY [14].
• Nevertheless, both control and CY-treated AML cells demonstrated similar dose-dependent sensitivity to 100 to 500 mumol/L phosphoramide mustard (PhM), the active alkylating end-product of CY activation in vivo [14].
• We compared the pharmacokinetics of daunomycin (7.5 mg/kg i.v. bolus injection) in normal and leukemic rats using a leukemia model which resembles acute myeloid leukemia in humans [15].
• Deoxycytidine kinase activity (dCk) was monitored in cell lines from a rat acute myeloid leukemia model of acquired resistance to cytosine arabinoside (AraC) and decitabine (DAC) [16].

Other interactions of Runx1

• Inhibition of OC transcription does not occur by a direct mechanism because in vitro methylated OC promoter DNA is still recognized by the key regulators Runx/Cbfa and the vitamin D receptor complex [17].
• Control and counter-control of TGF-beta activity through FAST and Runx (CBFa) transcriptional elements in osteoblasts [10].
• In vitro-induced resistance to the deoxycytidine analogues cytarabine (AraC) and 5-aza-2'-deoxycytidine (DAC) in a rat model for acute myeloid leukemia is mediated by mutations in the deoxycytidine kinase (dck) gene [18].
• DT388GMCSF, a fusion toxin composed of the NH2-terminal region of diphtheria toxin (DT) fused to human granulocyte-macrophage colony-stimulating factor (GMCSF) has shown efficacy in the treatment of acute myeloid leukemia [19].

Analytical, diagnostic and therapeutic context of Runx1

• Four AML1 transcripts are expressed in denervated muscle, and the abundance of each transcript increases after denervation [8].
• Further studies with this animal model of AML, in which resistance to CY is mediated by elevated ALDH activity, may elucidate mechanisms for effective elimination of drug-resistant leukemic cells ex vivo and in vivo [14].
• We have detected expression of DeltaTrkA in the original AML sample by reverse transcriptase PCR and by Western blot analysis [7].
• To study prognostic factors in infant acute myeloid leukemia (AML), we analyzed 44 children treated on Childrens Cancer Group protocols for MLL gene rearrangement by Southern blot, cytogenetic 11q23 abnormalities, and reactivity with monoclonal antibody 7 [20].
• We conclude that CFU-Leuk and CFU-GM assays are useful screening techniques to develop and evaluate strategies for ex vivo purging with chemotherapeutic agents in this preclinical model of autologous marrow transplantation for AML [21].

References