Prognostic and Therapeutic Value of Apolipoprotein A and a New Risk Scoring System Based on Apolipoprotein A and Adenosine Deaminase in Chronic Lymphocytic Leukemia.

Xiaoya Yun,Xinting Hu,Xin Wang,Zixun Yin,Huimin Zhang,Ming Liu,Xiang Sun,Xin Zhang,Ya Zhang

doi:10.3389/fonc.2021.698572

Abstract

Lipid metabolism is related to lymphomagenesis, and is a novel therapeutic target in some hematologic tumors. Apolipoprotein A (ApoA), the major protein of high-density lipoprotein (HDL), plays a crucial role in lipid transportation and protecting against cardiovascular disease, and takes effect on anti-inflammation and anti-oxidation. It is correlated with the prognosis of some solid tumors. Yet, there is no investigation involving the role of ApoA plays in chronic lymphocytic leukemia (CLL). Our retrospective study focuses on the prognostic value of ApoA in CLL and its therapeutic potential for CLL patients. Herein, ApoA is a favorable independent prognostic factor for both overall survival (OS) and progression-free survival (PFS) of CLL patients. ApoA is negatively associated with β2-microglobulin (β2-MG) and advanced stage, which are poor prognostic factors in CLL. Age, Rai stage, ApoA, and adenosine deaminase (ADA) are included in a new risk scoring system named ARAA-score. It is capable of assessing OS and PFS of CLL patients. Furthermore, cell proliferation assays show that the ApoA-I mimetic L-4F can inhibit the proliferation of CLL cell lines and primary cells. In conclusion, ApoA is of prognostic value in CLL, and is a potential therapy for CLL patients. The ARAA-score may optimize the risk stratification of CLL patients.

Highlights

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the proliferation of small and mature malignant Blymphocytes co-expressing CD5 and CD23 [1]
Our study showed the prognostic value of Apolipoprotein A (ApoA) in chronic lymphocytic leukemia (CLL) and the suppressive effect of ApoA on the proliferation of CLL cells for the first time
We found that ApoA was an independent prognostic factor for overall survival (OS) and progression-free survival (PFS) in CLL patients

Summary

INTRODUCTION

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the proliferation of small and mature malignant Blymphocytes co-expressing CD5 and CD23 [1]. Novel therapies improve the survival of CLL patients, such as the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and the B-cell lymphoma 2 (Bcl2) inhibitor venetoclax, high-risk CLL remains incurable [2,3,4,5]. CLL cells are like adipocytes rather than normal B-lymphocytes or other leukemia cells, producing energy by utilizing free fatty acids (FFA) [14]. The lipid-related pathway may be a potential target for novel CLL therapies. We conduct a retrospective study for the first time to investigate the effect that ApoA takes on the prognosis and therapy of CLL patients. The study investigates the association between ApoA and other clinical indicators of CLL patients. Our study may improve the risk stratification of CLL patients and provide a potential therapeutic target for them

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ETHICS STATEMENT