Genome sequencing of MLL-ENL transgenic Mus musculus

De-novo identification of secondary driver mutations in acute myeloid leukemia (AML) development was done in an inducible mouse model for MLL-ENL fusion gene. The activation of this oncogene has previously been shown to be sufficient to induce aggressive AML however there are indications of variations in disease on-set dependent which may reflect differences in the somatic mutational landscape. Here, pGMs with the fusion gene were sorted from donor mice and transplanted into multiple recipient mice thereafter leukemia was allowed to develop. Potential secondary mutations among somatic variants were filtered out for further validation.

本研究针对MLL-ENL融合基因构建诱导型小鼠模型，对急性髓系白血病（acute myeloid leukemia, AML）发生过程中的继发性驱动突变进行从头（de novo）鉴定。此前已有研究证实，该致癌基因的激活足以诱导侵袭性AML，但现有迹象表明，疾病发病存在异质性，这一现象可能反映了体细胞突变谱的差异。本研究中，我们从供体小鼠体内分选携带该融合基因的pGMs，并将其移植至多只受体小鼠体内，随后诱导白血病发生。我们对体细胞变异中的潜在继发性突变进行筛选，以开展后续验证实验。