t(8;21)(q22;q22), found in acute myeloid leukemia (AML) and occasionally in myelodysplasia (MDS), results in the fusion of the AML1 gene on 22q22 to the ETO gene on 8q22, generating a chimeric AML1/ETO transcript, which is a molecular marker of the translocation.
Our study demonstrates the potential of high-resolution array-based analysis and GEP and provides further evidence that AML with insertions generating the 5'RUNX1/3'RUNX1T1 fusion not only biologically resemble the t(8;21)(q22;q22)AML subgroup, but might also share its prognostically favorable clinical behavior.
The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect.
These findings suggested that P300 could be a therapeutic target and that C646 could be used as a potential treatment for RUNX1-ETO positive AML patients.
PEBP2alpha was found to be highly homologous to a Drosophila segmentation gene, runt, and a human gene AML1 that was identified as a part of the fusion gene, AML1/ETO (MTG8) generated by t(8;21) chromosome translocation associated with acute myelogenous leukemia (AML).
The induction of plakoglobin by AML fusion proteins led to downstream signaling and transactivation of TCF- and LEF-dependent promoters, including the c-myc promoter, which was found to be bound by plakoglobin in vivo after AML1-ETO expression. beta-Catenin protein levels and TCF and LEF target genes such as c-myc and cyclin D1 were found to be induced by the fusion proteins.
We serially monitored AML1-ETO fusion transcripts using RQ-PCR in 113 bone marrow or peripheral blood samples from 21 patients with AML1-ETO-positive acute myeloid leukemia and analyzed the prognostic relevance of the results.
Acute promyelocytic leukaemia (APL) with t(15;17);PML-RARα (n = 7/18; 39%) harboured the highest frequency of FLT3 mutations, followed by myelomonocytic (n = 4/18; 22%) and AML with t(8;21);RUNX1-RUNX1T1 (n = 2/21; 9%).
More importantly, coexpression of AML1-ETO and AML1-ETO9a results in the substantially earlier onset of AML and blocks myeloid cell differentiation at a more immature stage.
An AML1/ETO fusion transcript is consistently detected by RNA-based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation.
The translocation t(8;21)(q22;q22), which results in the fusion of the AML1 (RUNX1) and ETO (CBFA2T1) genes, is a recurrent aberration in acute myeloid leukemia (AML), preferentially correlated with FAB M2, and has the highest incidence in childhood AML.
To understand the contribution of the t(8;21) to AML, we transduced purified hematopoietic stem cells (HSC) with a retroviral vector that coexpressed AML1-ETO or just the AML1 portion (AML1d) of the translocation along with a green fluorescent protein reporter gene.
Rapid disappearance of AML1/ETO fusion transcripts in patients with t(8;21) acute myeloid leukemia following bone marrow transplantation and chemotherapy.
AML1-ETO down-regulates the transactivation capacity of PU.1 in myeloid U937 cells, and the expression levels of PU.1 target genes in AML French-American-British (FAB) subtype M2 patients with t(8;21) were lower than in patients without t(8;21).
Reciprocal RUNX1 fusions are traditionally found in up to 10% of acute myeloid leukemia (AML) patients, usually associated with a translocation (8;21)(q22;q22) corresponding to the RUNX1-RUNX1T1 fusion gene.