Identification of a Potently Oncogenic CALM-AF10 Minimal-Fusion Mutant (miRNA)

The t(10;11) p (13;q14) translocation, giving rise to CALM-AF10, is a recurring chromosomal translocation observed in several types of acute leukemias as well as in lymphoma. We have previously demonstrated that the expression of the human CALM/AF10 fusion gene in murine bone marrow stem and progenitor cells results in an aggressive acute myeloid leukemia in vivo. In this study, we have screened the various domains essential for CALM-AF10 function and leukemogenicity. Our study identifies a mutant of CALM-AF10 that greatly enhances the clonogenic potential of hematopoietic progenitors while retaining key characteristics of disease induced by the full length CALM-AF10 fusion. Global micro-RNA expression of bone marrow cells transduced with various constructs were compared. We used the empty vector, MIG, as a control and baseline. Four samples are tested with three biological replicates each.

t(10;11)(p13;q14)染色体易位可产生CALM-AF10融合基因，该易位是多种急性白血病及淋巴瘤中常见的复发性染色体异常。本团队此前已证实，将人源CALM-AF10融合基因在小鼠骨髓干细胞及祖细胞中表达，可在体内诱发侵袭性急性髓系白血病。本研究针对CALM-AF10功能与致白血病性所必需的各类结构域开展筛选，最终获得一种CALM-AF10突变体：该突变体可显著提升造血祖细胞的集落形成潜能，同时保留全长CALM-AF10融合蛋白所诱导疾病的核心特征。研究人员对经不同构建体转导的骨髓细胞进行了全基因组微小RNA（micro-RNA）表达谱比较，以空载体MIG作为对照与基线参照。本次实验共检测4份样本，每份样本均设置3次生物学重复。