FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia.
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.
Li
Fu Jun
FJ
Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, AL 35294-2182, USA.
Ding
Shouluan
S
Pan
Jicun
J
Shakhmatov
Mikhail A
MA
Kashentseva
Elena
E
Wu
Jiongru
J
Li
Yufeng
Y
Soong
Seng-jaw
SJ
Chiorazzi
Nicholas
N
Davis
Randall S
RS
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
D014408:Biomarkers, Tumor; C422179:FCRL2 protein, human; C457775:FCRL3 protein, human; C432367:FCRL5 protein, human; C452186:FCRLA protein, human; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D051746:ZAP-70 Protein-Tyrosine Kinase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1