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

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.

Distinct Age-Related Clinical Features and Risk Assessment in Chinese With Chronic Lymphocytic Leukemia

“…The aberrant regulation of apo A could be attributed to CLL pathogenesis. Previous studies have provided clues to the mechanisms underlying the prognostic values of apo A and HDL-C ( 29 , 30 ). Proteolytic products of apo A participate in anti-angiogenic and anti-tumoral activities ( 31 ).…”

Targeting metabolic reprogramming in chronic lymphocytic leukemia

“…Apolipoprotein A (ApoA) is one of the main components of HDL. A low level of ApoA is related to the advanced stage of CLL patients [ 56 ]. ApoA1 mimetics could inhibit the proliferation of CLL cells.…”

Validation and functional characterization of GWAS-identified variants for chronic lymphocytic leukemia: a CRuCIAL study

“…Recent studies have shown that increased serum levels of SIRT2 were associated with longer overall survival [ 5 ] whereas SIRT2 inhibitors induced cell death in leukemic cell lines [ 6 ]. Similarly, ADA, an enzyme of the purine metabolism related to lymphoid T cell differentiation and tumor cellular responses, has been found to be overexpressed in CLL patients and correlates with longer survival [ 7 ]. Another study showed that blockade of A2A adenosine receptors made CLL cells more susceptible to pharmacological treatments while restoring immune competence and T cell proliferation [ 8 ].…”

“…1E ), a key protein involved in the control of autophagy flux and the NLRP3 inflammasome. These results suggest that the GRAMD1B locus might exert its biological function on CLL by modulating SIRT2, STAMBP, and ADA, which is a diagnostic biomarker for CLL that has been included in a new prognosis score designed to optimize the patient risk stratification [ 7 ].…”