FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia.

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FCRL2 expression predicts IGHV mutation status and clinical progression in

chronic lymphocytic leukemia.

Fu Jun Li, Shouluan Ding, Jicun Pan, Mikhail A Shakhmatov, Elena Kashentseva,

Jiongru Wu, Yufeng Li, Seng-Jaw Soong, Chiorazzi, and Randall S

Blood, February 26, 2008;

Division of Hematology/Oncology, Department of Medicine, University of Alabama

at Birmingham, Birmingham, AL, United States.

CD38 and ZAP-70 are both useful prognostic markers for B cell chronic

lymphocytic leukemia (CLL), but are variably discordant with IGHV mutation

status. Five human Fc receptor-like (FCRL1-5) molecules 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

cases. FCRL1-3 and FCRL5 were found at markedly higher levels on CLL cells

bearing mutated IGHV genes than 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 to

76.6% for CD38 and 80.4% for ZAP-70. Compared to 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 to 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.

PMID: 18314442