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Published on: July 20, 2016
High CD49d protein and mRNA expression predicts poor outcome in chronic lymphocytic leukemia
Holger Nückel1, Magdalena Switala, Crista H Collins
1Department of Haematology, University of Duisburg-Essen, Germany. holger.nueckel@uni-due.de
Insights
High CD49d expression in B-cell chronic lymphocytic leukemia (B-CLL) patients indicates a poorer prognosis. This finding supports CD49d as a potential therapeutic target for B-CLL.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- CD49d is crucial for leukocyte function and cell interactions.
- Previous studies suggest prognostic relevance of CD49d in B-cell chronic lymphocytic leukemia (B-CLL).
- CD49d facilitates leukocyte trafficking, activation, and survival.
Purpose of the Study:
- To investigate the prognostic significance of CD49d protein and mRNA expression in B-CLL patients.
- To evaluate the association of CD49d expression with established prognostic markers.
- To explore CD49d as a potential therapeutic target in B-CLL.
Main Methods:
- Analyzed CD49d protein expression via flow cytometry in 101 CLL patients.
- Assessed CD49d mRNA levels.
- Correlated CD49d expression with treatment-free survival (TFS), overall survival (OS), CD38, ZAP-70, and IGVH mutation status.
Main Results:
- High CD49d protein expression (≥45%) was linked to significantly shorter TFS and OS.
- High CD49d expression correlated strongly with CD38 and ZAP-70 status.
- Multivariate analysis identified high CD49d expression as an independent prognostic factor.
Conclusions:
- CD49d expression is a significant independent prognostic factor in B-CLL.
- The study confirms the prognostic value of CD49d on both protein and mRNA levels.
- CD49d represents a promising molecular target for future B-CLL therapies.
Abstract:
CD49d plays a critical role in leucocyte trafficking, activation and survival, and facilitates interactions between leucocytes and stromal cells. Recent data give evidence for the prognostic relevance of CD49d protein expression in B-CLL. In our study we analyzed both the expression of CD49d protein and mRNA in a cohort of 101 CLL patients. The percentage of leukemic B-cells expressing CD49d determined by flow cytometry ranged from 0 to 100%. 37 patients with high CD49d protein expression >or=45% (according to ROC analysis) had a significantly shorter treatment-free survival (TFS) and overall survival (OS) than 64 patients with low CD49d expression (median TFS: 116 versus 43 months, p=0.015; median OS: not reached in both groups, p=0.018). CD49d protein expression was strongly associated with CD38 status (p=0.0001) and ZAP-70 status (p=0.03) but not with IGVH mutation. In multivariate analysis high CD49d expression was a significantly independent prognostic factor (HR 3.0; p=0.005). According to the strong correlation of CD49d protein expression with CD49d mRNA expression (r=0.39; p<0.0001) we could confirm the results on mRNA level with worse prognosis for patients with high mRNA level. Collectively, our data confirm the prognostic significance supporting the idea to use CD49d as target molecules for therapeutic approaches in B-CLL.
