Maffei Rossana, Fiorcari Stefania, Martinelli Silvia, Benatti Stefania, Bulgarelli Jenny, Rizzotto Lara, Debbia Giulia, Santachiara Rita, Rigolin Gian Matteo, Forconi Francesco, Rossi Davide, Laurenti Luca, Palumbo Giuseppe A, Vallisa Daniele, Cuneo Antonio, Gaidano Gianluca, Luppi Mario, Marasca Roberto
a Division of Hematology, Department of Medical and Surgical Sciences , University of Modena and Reggio Emilia , Modena , Italy.
b Immunotherapy Unit , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
Leuk Lymphoma. 2018 Feb;59(2):423-433. doi: 10.1080/10428194.2017.1339872. Epub 2017 Jun 22.
Lenalidomide is a therapeutically effective drug in chronic lymphocytic leukemia (CLL). Twenty-seven CLL patients were treated with lenalidomide in a phase II clinical trial. Ten patients were grouped as responders (R) and 6 as nonresponders (NR). We evaluated T lymphocytes, NK, monocytes and dendritic cells at baseline and after treatment. A gene expression analysis was performed on 16 CLL samples collected before treatment. The levels of immune cells or immune-related cytokines are not different between R and NR patients. However, CLL patients sensitive to lenalidomide clearly show a peculiar gene expression profile in leukemic cells. The most up-regulated gene (fold change = +23 in R vs. NR) is Wnt inhibitor SHISA homolog 3 (SHISA3). SHISA3CLL are characterized by a restrained activation of Wnt signaling and sensibility to lenalidomide-induced apoptosis. In conclusion, SHISA3 is a candidate gene for the identification of CLL patients who will benefit of lenalidomide treatment as single agent.
来那度胺是治疗慢性淋巴细胞白血病（CLL）的一种有效药物。在一项II期临床试验中，27例CLL患者接受了来那度胺治疗。10例患者被归为反应者（R）组，6例为无反应者（NR）组。我们在基线和治疗后评估了T淋巴细胞、自然杀伤细胞（NK）、单核细胞和树突状细胞。对治疗前收集的16份CLL样本进行了基因表达分析。R组和NR组患者的免疫细胞或免疫相关细胞因子水平没有差异。然而，对来那度胺敏感的CLL患者在白血病细胞中明显表现出一种特殊的基因表达谱。上调最明显的基因（R组与NR组的倍数变化=+23）是Wnt抑制剂SHISA同源物3（SHISA3）。SHISA3在CLL中的特征是Wnt信号通路的激活受到抑制以及对来那度胺诱导的凋亡敏感。总之，SHISA3是用于识别将从单用来那度胺治疗中获益的CLL患者的一个候选基因。
