lncRNA and mRNA Expression Profiling in Early Stage UM CLL

Predicting disease progression in chronic lymphocytic leukemia (CLL) remains challenging particularly in patients with Rai Stage 0/I disease that have an unmutated immunoglobulin heavy chain variable region (UM IGHV). Even though patients with UM IGHV have a poor prognosis and generally require earlier treatment, not all UM IGHV patients experience more rapid disease progression with some remaining treatment free for many years. This observation suggests biologic characteristics other than known prognostic factors influence disease progression. Alterations in long non-coding RNA (lncRNA) expression levels have been implicated in diagnosis and prognosis of various cancers, however, their role in disease progression of early Rai stage UM CLL is unknown. Here we use microarray analysis to compare lncRNA and mRNA profiles of Rai 0/I UM IGHV patients who progressed in <2 years relative to patients who had not progressed for >5 years. Over 1300 lncRNAs and 940 mRNAs were differentially expressed (fold change ≥ 2.0; p-value ≤ 0.05). Of interest, the differentially expressed lncRNAs G047155, TCAM1P, and uc.436, have known associated genes that have been linked to CLL. Thus, our study reveals differentially expressed lncRNAs in progressive early stage CLL requiring therapy versus indolent early Rai stage UM CLL. These lncRNAs have the potential to impact relevant biological processes and pathways that influence clinical outcome in CLL. Two-condition experiment, Progressive disease (PD) early Rai (0/I) Stage UM CLL (n=34) and Indolent disease (ID) early Rai (0/I) Stage UM CLL (n=29). One replicate per array.

预测慢性淋巴细胞白血病（chronic lymphocytic leukemia, CLL）的疾病进展仍颇具挑战，尤其针对Rai 0/I期且免疫球蛋白重链可变区未突变（unmutated immunoglobulin heavy chain variable region, UM IGHV）的患者。尽管UM IGHV型患者预后较差，通常需更早启动治疗，但并非所有此类患者的疾病进展都更为迅速，部分患者可多年无需接受治疗。这一观察结果提示，除已知预后因素外，尚有其他生物学特征影响CLL的疾病进程。

长链非编码RNA（long non-coding RNA, lncRNA）表达水平的改变已被证实与多种癌症的诊断及预后密切相关，但其在早期Rai分期UM IGHV型CLL疾病进展中的作用仍不明确。本研究采用基因芯片分析技术，对比了<2年内出现疾病进展的Rai 0/I期UM IGHV型CLL患者，与疾病无进展时长超过5年的同类型患者的lncRNA及信使RNA（mRNA）表达谱。最终鉴定出1300余种差异表达的lncRNA以及940余种差异表达的mRNA（倍数变化≥2.0；p值≤0.05）。值得关注的是，差异表达的lncRNA G047155、TCAM1P及uc.436，其已知的关联基因已被证实与CLL相关。因此，本研究揭示了需接受治疗的进展性早期CLL与惰性早期Rai 0/I期UM IGHV型CLL之间存在差异表达的lncRNA。此类lncRNA或可通过调控相关生物学过程及通路，进而影响CLL的临床转归。

本实验包含两种处理条件：进展性疾病（Progressive disease, PD）组早期Rai 0/I期UM IGHV型CLL患者（n=34），以及惰性疾病（Indolent disease, ID）组早期Rai 0/I期UM IGHV型CLL患者（n=29），每张芯片对应一个生物学重复。