我们报导PIM1激酶在慢性淋巴细胞白血病(CLL)/小淋巴细胞淋巴瘤(SLL)患者的淋巴细胞中表达。槲皮素,一种天然存在的类黄酮,是一种膳食补充剂,抑制许多激酶,包括PIM1,在体外。根据机构审查委员会批准的协议,我们表演了一个开放标签,单臂先导研究评估槲皮素对CLL/SLL患者的抗肿瘤活性。Q-ForceTM咀嚼物口服给药,500毫克,每天两次,三个月。符合条件的患者先前治疗失败,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反应。如果患者的淋巴细胞计数升高且≥10,000/µL但不>100,000/µL,则将其包括在内。3例患者接受槲皮素治疗。没有毒性。两个响应稳定的淋巴细胞计数上升(每个p<0.001),在随访期间保持稳定(停止治疗后5个月和11个月,分别)。无反应者中的CLL细胞具有TP53突变。尽管我们从这项初步转化研究中获得的数据是基于一个小样本,在选定的CLL/SLL患者中,槲皮素作为潜在治疗药物的进一步研究似乎有必要.
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-ForceTM 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/µL but not > 100,000/µL. 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.