Department of Medicine, UT Southwestern Medical Center, Dallas, USA.
Department of Medicine, Department of Hematology and Oncology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Leuk Res. 2021 Jan;100:106480. doi: 10.1016/j.leukres.2020.106480. Epub 2020 Nov 22.
Central nervous system (CNS) involvement in patients with acute myeloid leukemia (AML) varies, ranging from 0.6%-46%. Leukocyte immunoglobulin-like receptor B4 (LILRB4) has been shown to be critical in orchestration of infiltration of AML cells into the CNS in animal models, however it is unknown if an association exists between LILRB4 and CNS involvement (CNS+) in human patients with AML. LILRB4 was measured by flow cytometry in a heterogeneous population of fifty-six AML patients. Patients were then followed clinically for the development of CNS + . LILRB4 was positive in 91 % of patients with CNS + compared to 38 % without CNS involvement (p < 0.002). In logistic analysis: age, BMI, serum albumin and positive LILRB4 were predictive for CNS+ [OR, 95 % CI, p-value]: 0.95, 0.92-0.99, p < 0.01; 0.85, 0.73-0.998, p < 0.05; 0.23, 0.066-0.78, p < 0.02; 16.46, 1.93-140.2, p < 0.02, respectively. This finding of the association of LILRB4 with CNS + in combination with earlier findings suggests that LILRB4 has a mechanistic role in infiltration of the CNS and may provide insight into the pathogenesis of AML seeding the CNS. Moreover, this proof of concept and the findings in the present study may lead to the development of innovative and novel therapies to improve the lives of patients with AML.
中枢神经系统(CNS)在急性髓系白血病(AML)患者中的受累程度不一,范围从 0.6%到 46%。白细胞免疫球蛋白样受体 B4(LILRB4)已被证明在动物模型中对 AML 细胞浸润 CNS 起着关键作用,然而,在 AML 患者中,LILRB4 是否与 CNS 受累(CNS+)之间存在关联尚不清楚。在 56 例 AML 患者的异质性人群中通过流式细胞术测量 LILRB4。然后对患者进行临床随访,以观察 CNS+的发展情况。与无 CNS 受累的患者(38%)相比,CNS+患者的 LILRB4 阳性率为 91%(p < 0.002)。在逻辑分析中:年龄、BMI、血清白蛋白和阳性 LILRB4 是 CNS+的预测因素[OR,95%CI,p 值]:0.95,0.92-0.99,p < 0.01;0.85,0.73-0.998,p < 0.05;0.23,0.066-0.78,p < 0.02;16.46,1.93-140.2,p < 0.02。LILRB4 与 CNS+的这种关联的发现,结合早期的发现,表明 LILRB4 在 CNS 浸润中具有机制作用,并可能为 AML 播散到 CNS 的发病机制提供深入了解。此外,本研究的这一概念验证和发现可能会导致开发创新和新型疗法,以改善 AML 患者的生活。