LPL and ADAM-29 Gene Expressions Stratify Prognosis in Clinical Stage BinetA and B Chronic Lymphocytic Leukemia Patients

Abstract

Introduction: Chronic Lymphocytic Leukemia (CLL) is the most frequent adult leukemia in western countries. It is known to have a heterogeneous clinical course, some patients presenting an indolent disease while others have an aggressive disease requiring prompt treatment. Therefore, an individualized approach, especially in early clinical stage patients is necessary. Recent studies suggest that the biological markers LPL and ADAM-29 could be useful to predict prognosis in CLL patients: LPL being associated with an unfavorable prognosis while ADAM-29 to favorable one. Aims: to evaluate the expression of LPL (L), ADAM-29 (A) and the L/A ratio in CLL patients in regard to Binet clinical stage and progression free survival (PFS). Patients and Methods: thirty CLL patients followed at UNIFESP/EPM and HSPE were studied. RNA extraction was done by the TRIZOL method followed by c-DNA synthesis. c-DNA was amplified by PCR using LPL and ADAM-29 specific primers. T-Student’s exact test was used to compare the genes frequencies and Kaplan Meyer analysis to evaluate PFS. The results were considered statistically significant when p<0.05. Results: Of the 30 CLL patients studied (16M/14F, median age of 67 years, varying from 38 to 64 years) 19 (63,3%) were early clinical stage (Binet A), 8 (26,7%) Binet B and 3 (10%) Binet C. In the Binet A group LPL was negative in 52.63% of the patients and ADAM-29 positive in 63.15% with relation LPL-/ADAM29+ (or L/A=0) in 52.63% (10/19). In contrast among Binet B and C patients 90% (10/11) presented relation LPL+/ADAM-29- (or L/A=1). Those who were LPL+ or ADAM-29- or L/A=1 had a shorter PFS when compared to those LPL-or ADAM-29+ or L/A=0 (p<0.05). Patients, even those in early clinical stages (Binet A and B), when LPL+, ADAM- and L/A=1 constitute a group with an unfavorable prognosis with a short DFPS (p<0.05). Conclusion: Our study shows that patients with a positive expression of LPL, negative for ADAM-29 and with L/A=1 have unfavorable prognosis independent of clinical stage. Analyzing Binet A and B together, we identified a subgroup LPL+, ADAM- and L/A=1 with a poor outcome. Thus, the expression profile of these genes could be useful to identify Binet A and B patients with an unfavorable prognosis, contributing to the decision making process to begin therapy in an individualized manner. (Support–FAPESP proc n. 05/57792-0)