Trissal Maria C, DeMoya Ricardo A, Schmidt Amy P, Link Daniel C
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
PLoS One. 2015 Mar 20;10(3):e0119304. doi: 10.1371/journal.pone.0119304. eCollection 2015.
MIR233 is genetically or epigenetically silenced in a subset of acute myeloid leukemia (AML). MIR223 is normally expressed throughout myeloid differentiation and highly expressed in hematopoietic stem cells (HSCs). However, the contribution of MIR223 loss to leukemic transformation and HSC function is largely unknown. Herein, we characterize HSC function and myeloid differentiation in Mir223 deficient mice. We show that Mir223 loss results in a modest expansion of myeloid progenitors, but is not sufficient to induce a myeloproliferative disorder. Loss of Mir223 had no discernible effect on HSC quiescence, long-term repopulating activity, or self-renewal capacity. These results suggest that MIR223 loss is likely not an initiating event in AML but may cooperate with other AML associated oncogenes to induce leukemogenesis.
MIR233在一部分急性髓系白血病（AML）中通过基因或表观遗传方式沉默。MIR223在整个髓系分化过程中正常表达，并在造血干细胞（HSC）中高表达。然而，MIR223缺失对白血病转化和HSC功能的影响在很大程度上尚不清楚。在此，我们对Mir223缺陷小鼠的HSC功能和髓系分化进行了表征。我们发现Mir223缺失导致髓系祖细胞适度扩增，但不足以诱发骨髓增殖性疾病。Mir223的缺失对HSC静止、长期重建活性或自我更新能力没有明显影响。这些结果表明，MIR223缺失可能不是AML的起始事件，但可能与其他AML相关癌基因协同作用以诱导白血病发生。
