FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia |
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Authors: | Li Fu Jun Ding Shouluan Pan Jicun Shakhmatov Mikhail A Kashentseva Elena Wu Jiongru Li Yufeng Soong Seng-jaw Chiorazzi Nicholas Davis Randall S |
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Institution: | 1 Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham; 2 Comprehensive Cancer Center, University of Alabama at Birmingham; 3 Laboratory of Experimental Immunology, The Feinstein Institute for Medical Research, North Shore–Long Island Jewish Health System, Manhasset, NY; 4 Departments of Cell Biology and Medicine, Albert Einstein College of Medicine, Bronx, NY; 5 Department of Microbiology, University of Alabama at Birmingham; and 6 Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham |
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Abstract: | CD38 and ZAP-70 are both useful prognostic markers for B-cell chronic lymphocytic leukemia (CLL), but are variably discordant with IGHV mutation status. A total of 5 human Fc receptor–like molecules (FCRL1-5) have tyrosine-based immunoregulatory potential and are expressed by B-lineage subpopulations. To determine their prognostic potential in CLL, FCRL expression was compared with IGHV mutation status, CD38 and ZAP-70 expression, and clinical features from 107 patients. FCRL1, FCRL2, FCRL3, and FCRL5 were found at markedly higher levels on CLL cells bearing mutated IGHV genes than on unmutated CLL cells or CD19+ polyclonal B lymphocytes. Univariate comparisons found that similar to CD38 and ZAP-70, FCRL expression was strongly associated with IGHV mutation status; however, only FCRL2 maintained independent predictive value by multivariate logistic analysis. Strikingly, FCRL2 demonstrated 94.4% concordance with IGHV mutation compared with 76.6% for CD38 and 80.4% for ZAP-70. Compared with other indicators, FCRL2 was also superior at predicting the time to first therapy; the median treatment-free interval was 15.5 years for patients with high FCRL2 expression compared with 3.75 years for FCRL2-low patients. Our studies indicate that FCRL2 has robust predictive value for determining IGHV gene mutation status and clinical progression and thus may further improve prognostic definition in CLL. |
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