Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage

Abstract

The aim of the present study was to investigate different biological prognostic markers to identify high-risk patients with chronic lymphocytic leukemia (CLL) with a higher tumor burden, in order to ensure appropriate management. A total of 81 Egyptian patients with CLL were enrolled in the present study, with 75 healthy subjects serving as the control group. The expression of CD49d, CD38 and ZAP-70 in CLL cells was assessed using flow cytometry. The fluorescence in situ hybridization technique was employed to evaluate TP53 (del17p), ataxia-telangiectasia (del11q) and 13q14 (del13q14) genes and the presence of trisomy 12. The serological markers β2 microglobulin (B2M) and sCD23 were measured by ELISA. The CD49d gene was highly expressed in 25.9% and cytogenetic aberrations were observed in 66.6% of all recruited CLL patients. The patients were categorized according to the Binet staging system and a significant increase in the expression of sCD23, CD49d and ZAP-70 was detected in group C (P=0.008, 0.034 and 0.017, respectively) when compared to groups A and B. CD49d + patients exhibited significantly higher expression of CD38 (P=0.002) and trisomy 12 (P=0.015) and lower expression of del13q14 (P=0.001). Patients who were CD49d + with B2M>3.5 µg/ml exhibited higher total leukocyte count (P=0.048), higher absolute lymphocyte count (P=0.036), higher expression of CD38 (P=0.002) and trisomy 12 (P=0.034) and lower expression of del13q14 (P=0.002). Therefore, sCD23, CD49d and ZAP-70 may be considered as an optimal prognostic marker combination to be evaluated in the early stages of CLL and throughout disease management. Integrating both serological markers and CD49d expression by flow cytometry may add to the prognostic value of each marker alone and help identify high-risk patients with a higher tumor burden.

Immunophenotypic Characterization by Flow Cytometry of Chronic Lymphoid Leukemia

“…It is a critical regulator of CLL cell migration, allowing tumor cells to pass from the blood to the protective microenvironment of LN and BM. [46] The high level in patients with B-CLL is associated with an aggressive course of the disease and is considered one of the negative prognostic markers [47]. In this series of cases, it was found that 65.6% of the patients expressed CD49d, results that coincide with those of the study carried out by Al-Rubaie HA et al [48] in Iraq that showed positivity for CD49d (60%).…”

Expression of ZAP 70 in Chronic Lymphocytic Leukemia (CLL) and its Correlation with Clinical Stages

“…Out of total 10/73 (13.4%) patients 4 (40%) showed positive results and 6 (60%) negative results. Attia HR et al, 18 documented in their study that in the Binet staging system, there was a noteworthy increase in the expression of ZAP-70 in group C patients compared to groups A and B (p-value 0.008, 0.034 and 0.017 respectively ) which were linked to higher CD38 expression, hepatomegaly, splenomegaly, and specific genetic markers. This study showed a more comprehensive analysis of prognostic markers with males being more prevalent as in our study.…”