AML1-ETO needs a partner: new insights into the pathogenesis of t(8;21) leukemia.
The detailed characterization of genetic and molecular aberrations in acute myeloid leukemia (AML) has substantially improved our understanding of the pathogenesis of this disease. With an incidence of up to 12% in all AML cases, the translocation t(8;21), forming the AML1-ETO fusion gene, is one of the most common genetic aberrations in AML. Experimental data have shown that AML1-ETO is not sufficient to induce leukemia by itself, but has to collaborate with other genetic alterations for leukemic transformation. These data are supported by observations in AML patients, who recurrently show activating mutations of the receptor tyrosine kinase FLT3 or c-KIT together with the AML1-ETO fusion gene. These findings might have clinical implications and provide a rationale to test RTK inhibitors in the treatment of patients with core binding factor AML and concurrent activating RTK mutations.
Kuchenbauer
F
F
Department of Internal Medicine III, Ludwig-Maximilians University of Munich, University Hospital Grosshadern, Munich, Germany.
Feuring-Buske
M
M
Buske
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C
D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000473:pathology*; D008957:Models, Genetic; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D014178:Translocation, Genetic / Q000235:genetics*
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein