NESCALM-AF10

NESCALM-AF10 is an experimental synthetic fusion protein designed to investigate the molecular mechanisms of leukemogenesis in CALM-AF10-positive hematopoietic malignancies, such as acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). It consists of an 18-amino acid peptide containing the nuclear export signal (NES) from the CALM protein fused in-frame to the AF10 protein. Research has demonstrated that the NES-mediated cytoplasmic localization of the fusion protein is essential for its oncogenic activity, which includes the upregulation of Hoxa cluster genes and the reduction of H3K79 methylation. This construct serves as a critical research tool to validate that nuclear export is a necessary and sufficient driver of CALM-AF10-mediated transformation, suggesting that nuclear export inhibitors (NEIs) could be potential therapeutic agents for these aggressive leukemias.