利用高通量单细胞RNA测序解析慢性粒单核细胞白血病特异分子标记物

慢性粒单核细胞白血病（CMML）是一种临床表现异质性较大的慢性骨髓增生异常/骨髓增殖性(MDS/MPD)疾病。虽然去甲基化药物（如阿扎胞苷和地西他滨）能够缓解约30%CMML患者的疾病进展，但是这类药物作用的肿瘤细胞类型、分子机制、和敏感患者特征仍不清楚。为了探索、开发新的CMML精准诊断与治疗方法，本研究将利用新一代高通量单细胞RNA测序技术来解析CMML细胞类型。通过比较正常人与去甲基化药物治疗前后CMML患者的外周血样本，我们将在单细胞水平上阐明CMML细胞特异的基因表达谱，以及去甲基化药物作用的细胞类型与基因调控网络。在此基础之上，我们还将开发新的CMML细胞特异的免疫组化和流式分选方法，用于识别和跟踪治疗前后CMML细胞类型的演变过程。此项研究将有助于推动新型单细胞测序技术在肿瘤精准诊断与治疗中的应用。

Chronic myelomonocytic leukemia (CMML) is a heterogeneous type of myelodysplastic/myeloproliferative neoplasm. Although hypomethylation agents such as azacytidine and decitabine are used to treat CMML, they only temporarily relieve the tumor burden in approximately 30% of the patients and little is understood about the underlying mechanism. Here we aim to use high-throughput single-cell RNA sequencing technologies (scRNA-seq) to characterize CMML clinical samples. By analyzing the cellular composition of the peripheral blood mononuclear cells of CMML patients before and after hypomethylator treatment, we will define the genes and gene-sets that are unique to CMML, as well as those responding to hypomethylators. Based on this analysis, we will further develop highly specific immunohistochemistry and flow cytometry methods to identify CMML cells. Our study will pave the way for applying single cell sequencing technologies to improve precision therapy of hematopoietic neoplasms.