The association of leukocyte immunoglobulin-like receptor subfamily B-4 expression in acute myeloid leukemia and central nervous system involvement. (January 2021)

• Record Type: Journal Article
• Authors: Bergstrom, Colin P.; Dahiya, Saurabh; Chen, Weina; Zhang, Cheng Cheng; Zhu, Hong; Yan, Jingsheng; Madanat, Yazan; Patel, Prapti; Vusirkala, Madhuri; Ramakrishnan, Praveen; Rizvi, Syed; Chung, Stephen; Awan, Farrukh; Anderson, Larry D.; Collins, Robert; Kansagra, Ankit
• Is Part Of: Leukemia research. Volume 100(2021)
• Publication Date: 2021-01
• Subjects: Myeloid leukemias and dysplasias -- Clinical results -- Molecular genetics -- Prognostication; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2020.106480
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: LILRB4 is an immunoreceptor expressed on hematopoietic–lineage cells. LILRB4 in animal models was demonstrated to orchestrate infiltration into the CNS. LILRB4 was measured in human AML patients and they were followed for CNS disease. LILRB4 was associated with the subsequent development of CNS involvement. LILRB4 offers insight in the pathogenesis of AML seeding the CNS and novel therapies. Abstract: 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.