Comparison of human BCP-ALL MLL-r and normal CD19+CD10+ precursor B-cell transcriptomes

B-cell precursor acute lymphoblastic leukemia (pre-B ALL) with mixed-lineage leukemia gene rearrangement (MLL-r) is a poor-prognosis subtype for which additional therapeutic targets are needed. We evaluated the glycomes, transcriptomes and proteomes of the same samples using only about 10^6 cells for each assay. We found that the expression of many genes involved in glycosylation differ between MLL-r cells and normal controls: 61 of the 221 human glycosyltransferases were differentially expressed in MLL-r cells. The leukemia cell glycome and many proteins associated with glycan biosynthesis were also significantly changed compared to normal control precursor B-cells, indicating that the malignant phenotype of these cells could be regulated by such changes. Four bone marrow samples from different donors depleted of CD34+ stem cells were used to isolate normal healthy precursor CD19+CD10+ B-cells. Red blood cells were removed from three leukemic pre-B ALL MLLr bone marrow samples before RNA isolation.

伴有混合谱系白血病基因重排（MLL-r）的前体B细胞急性淋巴细胞白血病（pre-B ALL）是一类预后不良的亚型，亟需开发额外的治疗靶点。本研究针对同一份样本，针对每个检测项目仅使用约10^6个细胞，同步完成了糖组、转录组与蛋白质组的检测分析。研究发现，诸多参与糖基化过程的基因在MLL-r细胞与正常对照样本间存在表达差异：221个人类糖基转移酶中，有61个在MLL-r细胞内呈现差异表达。与正常对照的前体B细胞相比，白血病细胞的糖组特征以及诸多与聚糖生物合成相关的蛋白质均发生了显著改变，提示此类变化可能参与调控该类细胞的恶性表型。本研究纳入4份来自不同供体的骨髓样本，通过去除CD34阳性干细胞以分离得到正常健康的CD19阳性CD10阳性前体B细胞；同时收集3份白血病性pre-B ALL MLL-r骨髓样本，在提取RNA前先去除其中的红细胞。