Myb drives B-cell neoplasms and myeloid malignancies in vivo

作者：Tim Pieters, André Almeida, Sara T’Sas, Kelly Lemeire, Tino Hochepied, Geert Berx, Alex Kentsis, Steven Goossens, Pieter Van Vlierberghe · 发表于：Blood Advances · 年份：2022 · DOI：10.1182/bloodadvances.2021005955 · 被引用次数：12 · 研究领域：Chronic Lymphocytic Leukemia Research、Acute Myeloid Leukemia Research、Multiple Myeloma Research and Treatments

The proto-oncogene MYB encodes the transcription factor c-MYB (cellular MYB, hereafter called MYB), which is often upregulated or aberrantly activated in cancer, including hematological malignancies.1,2 High Myb levels were especially found in acute myeloid leukemia (AML).2-4 Myb was identified initially as a retroviral oncogene (v-Myb) of avian myeloblastosis virus and E26.5,6 These retroviruses are able to transform immature hematopoietic cells in vitro and induce AMLs in chickens7 and mice.8 In leukemia patients, MYB is highly expressed, and in a subset of patients, this is a consequence of translocations, genomic duplications, or somatic mutations that involve the MYB gene itself.9-12 Furthermore, compelling evidence is accumulating that MYB also acts as a dependency factor for the maintenance of most myeloid, T-, and B-cell leukemias.13-15 Overexpression of viral MYB, a truncated form of MYB that lacks its negative regulatory domain, results in the spontaneous formation of T-cell lymphomas in mice.16 However, the in vivo roles of cellular MYB in tumor initiation remain largely unexplored. Here, we show, for the first time, that hematopoietic-specific overexpression of Myb is sufficient to drive B-cell neoplasms and myeloid malignancies in mice. To evaluate whether elevated MYB expression is sufficient to transform cells in vivo, we developed a conditional Myb overexpression (R26-Myb) mouse model (Figure 1A; supplemental Figure 1A,B) using an optimized pipeline for target...