Quercetin Therapy for Selected Patients with PIM1 Kinase-Positive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pilot Study
Quercetin Therapy for Selected Patients with PIM1 Kinase-Positive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pilot Study
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DOI：
10.1159/000486361
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发表时间：
2018-01-01
影响因子：
2.4
通讯作者：
Baron, Joseph M.
中科院分区：
文献类型：
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作者：
Baron, Beverly W.;Thirman, Michael J.;Baron, Joseph M.
我们报道了PIM1激酶在慢性淋巴细胞白血病(CLL)/小淋巴细胞性淋巴瘤(SLL)患者淋巴细胞中的表达。槲皮素是一种天然的类黄酮类化合物，是一种膳食补充剂，在体外可以抑制包括PIM1在内的许多激酶。根据机构审查委员会批准的方案，我们进行了一项开放标记的单臂先导性研究，以评估Qercetin在CLL/SLL患者中的抗肿瘤活性。Q-Force(TM)咀嚼片口服，每天两次，500毫克，为期3个月。符合条件的患者以前的治疗失败，没有其他标准治疗，或拒绝其他治疗。根据疾病参数的客观变化评估疗效。如果患者的淋巴细胞计数上升，且L=10,000/亩，而不是100,000/亩·L，则纳入其中。3名患者接受了槲皮素治疗。没有毒性。两人的反应是淋巴细胞计数稳定上升(P<；每人0.001)，在他们的随访期间(分别在停止治疗后5个月和11个月)保持稳定。无反应者体内的CLL细胞含有TP53突变。尽管我们的这项先导性翻译研究的数据是基于一个小样本，但是进一步研究在选定的慢性淋巴细胞性白血病/系统性红斑狼疮患者中作为潜在的治疗剂似乎是合理的。(C)2018年S.Karger AG，巴塞尔
We reported that PIM1 kinase is expressed in the lymphocytes of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Quercetin, a naturally occurring flavonoid, is a dietary supplement and inhibits many kinases, including PIM1, in vitro. Under an Institutional Review Board-approved protocol, we performed an open-label, single-arm pilot study to evaluate the antitumor activity of quercetin in patients with CLL/SLL. Q-Force (TM) chews were administered orally, 500 mg twice daily, for 3 months. Eligible patients had failed prior therapies, had had no other standard treatment, or refused other therapies. Response was assessed based on objective change in disease parameters. Patients were included if their lymphocyte counts were rising and >= 10,000/mu L but not > 100,000/mu L. Three patients received quercetin treatment. There was no toxicity. Two responded with stabilization of rising lymphocyte counts (p < 0.001 for each), which remained stable during their follow-up (5 and 11 months after cessation of treatment, respectively). The CLL cells in the nonresponder harbored a TP53 mutation. Although our data from this pilot translational study are based on a small sample, further studies of quercetin as a potential therapeutic agent in selected patients with CLL/SLL appear warranted. (C) 2018 S. Karger AG, Basel