Forced expression of AML1-AMP19, a fusion transcript generated from a radiation-associated t(19;21) leukemia, blocks myeloid differentiation.
We isolated and characterized a novel AML1 (also termed Runx1) fusion transcript from a radiation-associated acute myeloid leukemia with a t(19;21). This fusion transcript, termed AML1-AMPl9, was joined out of frame, resulting in a truncated AML1 protein that inhibits activation of AML1 target promoters. It is now becoming clear that truncations of AMLl are more common in leukemia than previously thought. To analyze the effect of truncated AML1 species on myeloid differentiation and proliferation, AML1-AMPl9 was retrovirally transduced into the IL-3-dependent 32D cells. 32D cells over-expressing AML1-AMPl9 failed to differentiate normally when stimulated with G-CSF, but continued to proliferate and maintained a primitive phenotype. However, AML1-AMPl9 did not transform the cells to cytokine independence, implying that for full transformation of a myeloid progenitor by truncated AML1 another genetic lesion is required.
Ramsey
Heather
H
Cancer Research and Treatment Center, University of New Mexico Health Science Center, 900 Camino de Salud, Albuquerque, NM 87131, USA.
Christopherson
Kent
K
Hromas
Robert
R
D002453:Cell Cycle; D002454:Cell Differentiation; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D013234:Stem Cells; D014178:Translocation, Genetic / Q000235:genetics*
C424128:AML1-AMP19 fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D016207:Cytokines; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor