Nuclear export signal within CALM is necessary for CALM-AF10-induced leukemia.
Bottom Line: The CALM-AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies.Mutations in the NES eliminated the capacity of CALM-AF10 to immortalize murine bone-marrow cells in vitro and to promote development of acute myeloid leukemia in mouse models.These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm.
Affiliation: Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.Show MeSH
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Mentions: It has been reported that CALM-AF10 interacts with the histone methyltransferase DOT1L to mediate H3K79 hypermethylation at the Hoxa5 locus.9 To determine whether Dot1L colocalizes with CALM-AF10 and NES2-AF10 in the leukemia cells, we performed immunofluorescence analysis. Dot1L mainly localized in the nucleus while CALM-AF10 and NES2-AF10 mainly localized in the cytoplasm (Fig.5a,b). Dot1L partially colocalized with both CALM-AF10 and NES2-AF10, but neither CALM-AF10 nor NES2-AF10 altered the localization of Dot1L (Fig.5a).
Affiliation: Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.