Porter Shaina N, Magee Jeffrey A
Division of Pediatric Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
Division of Pediatric Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
Exp Hematol. 2017 Sep;53:43-47. doi: 10.1016/j.exphem.2017.05.006. Epub 2017 Jun 6.
Acute myeloid leukemia (AML) cells often co-opt normal hematopoietic stem cell (HSC) programs to drive neoplastic proliferation, and HSC-related gene expression signatures have been identified as biomarkers for poor prognosis in AML patients. We sought to identify new regulators of HSCs and AML cells from previously published HSC and leukemia stem cell (LSC) gene expression signatures. We identified PRKCH (protein kinase C eta) as a gene that is highly expressed in both mouse and human HSCs, as well as in LSCs from independent cohorts of AML patients. Prkch deletion in mice resulted in impaired HSC function. PRKCH was most highly expressed in undifferentiated (FAB M0) subtype AML, and high expression correlated with TP53 and RUNX1 mutations, high-risk cytogenetic features, and poor overall survival. Prkch deletion in an Flt3-ITD/Runx1 mutant mouse AML model did not extend survival. Thus, PRKCH is necessary for normal HSC function; its expression predicts poor survival in AML patients, but it is not required for AML to develop.
急性髓系白血病（AML）细胞常利用正常造血干细胞（HSC）程序来驱动肿瘤增殖，并且与HSC相关的基因表达特征已被确定为AML患者预后不良的生物标志物。我们试图从先前发表的HSC和白血病干细胞（LSC）基因表达特征中鉴定HSC和AML细胞的新调节因子。我们鉴定出PRKCH（蛋白激酶C eta）是在小鼠和人类HSC以及来自独立AML患者队列的LSC中均高表达的基因。小鼠中Prkch基因缺失导致HSC功能受损。PRKCH在未分化（FAB M0）亚型AML中表达最高，其高表达与TP53和RUNX1突变、高危细胞遗传学特征以及总体生存率低相关。在Flt3-ITD/Runx1突变小鼠AML模型中删除Prkch并不能延长生存期。因此，PRKCH对于正常HSC功能是必需的；其表达预示AML患者生存率低，但它不是AML发生所必需的。
