EXPRESSION OF FCGAMMARIIB PREDICTS TIME TO TREATMENT IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Bosch R. 06/09/16; 132589; E1040
Dr. Rosa Bosch
Contributions
Contributions
Abstract
Abstract: E1040
Type: Eposter Presentation
Background
The Fcγ receptor IIb (FcγRIIb) is a low-affinity Fcγ receptor that negatively regulates B-cell receptor (BCR) function in normal B-cells. In chronic lymphocytic leukemia (CLL) cells, FcγRIIb may exert this inhibitory effect when colligated with the BCR. Since CLL cells are activated in vivo, the clinical impact of FcγRIIb expression in this malignancy is worth of being investigated.
Aims
The aims of this study were to: (1) analyze the basal expression of FcγRIIb on CLL cells and normal B-cells; (2) investigate the relationship between FcγRIIb and well-known prognostic markers; and (3) explore the prognostic impact of FcγRIIb on clinical outcome of patients with CLL.
Methods
The study population included 174 patients with active CLL and 34 healthy donors. The median age at diagnosis was 66 years (34-88) and follow-up was 8.0 years (0-38.7). FcγRIIb expression was determined by flow cytometry using an Alexa488-conjugated mAb specific for human FcγRIIb within the following combinations: FcγRIIb/CD38/CD19/CD5 and FcγRIIb/CD49d/CD19/CD5. Results were expressed as the ratio between the MFI for FcγRIIb and the MFI for the corresponding isotype (MFIR). The Fisher’s exact test and the Mann-Whitney U test were used for comparisons between groups. Kaplan–Meier survival and Cox regression analysis were performed to evaluate the correlation of FcγRIIb expression with clinical outcome. Best cut-offs for time to treatment (TTT) were determined by ROC curves.
Results
Both CD5+CD19+ leukemic cells and CD19+ normal B-cells expressed FcγRIIb, with no significant differences in MFIR between the populations [median MFIR: 46.4 (8.3-153.4) vs 49.4 (30.8-73.2), p=0.812]. FcγRIIb expression, however, was highly heterogeneous among CLL samples, with 4.5% showing very high expression (outliers). Within clones from the same patient, FcγRIIb MFIR was higher on CD38+ or CD49d+ cells than on CD38- or CD49d- cells, respectively (p<0.01). Eighty-one percent (142/174) of patients showed high (MFIR>30.8) and 19% had low FcγRIIb expression (MFIR<30.8). We did not find any association between FcγRIIb expression and well-known prognostic markers except CD49d (p=0.025). However, the correlation between FcγRIIb and CD49d expression was very weak (κ=0.085) showing concordance in only 39.7% of cases. At the time of analysis, 52 patients (29.9%) had required therapy. Patients with low FcγRIIb expression had a significantly shorter TTT than those with high FcγRIIb expression (median 46.07 vs 62.7 months; log-rank p<0.028). In univariate analysis, other prognostic parameters, such as clinical stage, serum B2M, elevated LDH, ZAP70, CD38 and CD49d expression, IGHV mutational status, cytogenetics, and mutations of NOTCH1 and SF3B1 significantly correlated with shorter TTT (p<0.01). In a multivariate analysis incorporating FcγRIIb expression, ZAP70, CD38 and CD49d expression, IGHV mutational status, cytogenetics, and mutations of NOTCH1 and SF3B1, only low FcγRIIb expression (HR 2.66, 95%CI 1.22-5.80, p=0.014), unmutated IGHV (HR 3.02, 95%CI 1.30-7.02, p=0.010), and mutated SF3B1 (HR 11.27, 95% CI 2.82-45.12, p=0.001) and NOTCH1 (HR 4.79, 95%CI 1.31-17.48, p=0.018) retained prognostic significance for shorter TTT.
Conclusion
FcγRIIb expression can predict time to treatment in CLL, underlying a key role of the receptor in the progression of this malignancy. These results encourage further investigation to characterize the mechanisms by which FcγRIIb controls CLL cell activation and to uncover the relationship of FcγRIIb with other molecules, particularly CD49d.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Fc receptor, Treatment
Type: Eposter Presentation
Background
The Fcγ receptor IIb (FcγRIIb) is a low-affinity Fcγ receptor that negatively regulates B-cell receptor (BCR) function in normal B-cells. In chronic lymphocytic leukemia (CLL) cells, FcγRIIb may exert this inhibitory effect when colligated with the BCR. Since CLL cells are activated in vivo, the clinical impact of FcγRIIb expression in this malignancy is worth of being investigated.
Aims
The aims of this study were to: (1) analyze the basal expression of FcγRIIb on CLL cells and normal B-cells; (2) investigate the relationship between FcγRIIb and well-known prognostic markers; and (3) explore the prognostic impact of FcγRIIb on clinical outcome of patients with CLL.
Methods
The study population included 174 patients with active CLL and 34 healthy donors. The median age at diagnosis was 66 years (34-88) and follow-up was 8.0 years (0-38.7). FcγRIIb expression was determined by flow cytometry using an Alexa488-conjugated mAb specific for human FcγRIIb within the following combinations: FcγRIIb/CD38/CD19/CD5 and FcγRIIb/CD49d/CD19/CD5. Results were expressed as the ratio between the MFI for FcγRIIb and the MFI for the corresponding isotype (MFIR). The Fisher’s exact test and the Mann-Whitney U test were used for comparisons between groups. Kaplan–Meier survival and Cox regression analysis were performed to evaluate the correlation of FcγRIIb expression with clinical outcome. Best cut-offs for time to treatment (TTT) were determined by ROC curves.
Results
Both CD5+CD19+ leukemic cells and CD19+ normal B-cells expressed FcγRIIb, with no significant differences in MFIR between the populations [median MFIR: 46.4 (8.3-153.4) vs 49.4 (30.8-73.2), p=0.812]. FcγRIIb expression, however, was highly heterogeneous among CLL samples, with 4.5% showing very high expression (outliers). Within clones from the same patient, FcγRIIb MFIR was higher on CD38+ or CD49d+ cells than on CD38- or CD49d- cells, respectively (p<0.01). Eighty-one percent (142/174) of patients showed high (MFIR>30.8) and 19% had low FcγRIIb expression (MFIR<30.8). We did not find any association between FcγRIIb expression and well-known prognostic markers except CD49d (p=0.025). However, the correlation between FcγRIIb and CD49d expression was very weak (κ=0.085) showing concordance in only 39.7% of cases. At the time of analysis, 52 patients (29.9%) had required therapy. Patients with low FcγRIIb expression had a significantly shorter TTT than those with high FcγRIIb expression (median 46.07 vs 62.7 months; log-rank p<0.028). In univariate analysis, other prognostic parameters, such as clinical stage, serum B2M, elevated LDH, ZAP70, CD38 and CD49d expression, IGHV mutational status, cytogenetics, and mutations of NOTCH1 and SF3B1 significantly correlated with shorter TTT (p<0.01). In a multivariate analysis incorporating FcγRIIb expression, ZAP70, CD38 and CD49d expression, IGHV mutational status, cytogenetics, and mutations of NOTCH1 and SF3B1, only low FcγRIIb expression (HR 2.66, 95%CI 1.22-5.80, p=0.014), unmutated IGHV (HR 3.02, 95%CI 1.30-7.02, p=0.010), and mutated SF3B1 (HR 11.27, 95% CI 2.82-45.12, p=0.001) and NOTCH1 (HR 4.79, 95%CI 1.31-17.48, p=0.018) retained prognostic significance for shorter TTT.
Conclusion
FcγRIIb expression can predict time to treatment in CLL, underlying a key role of the receptor in the progression of this malignancy. These results encourage further investigation to characterize the mechanisms by which FcγRIIb controls CLL cell activation and to uncover the relationship of FcγRIIb with other molecules, particularly CD49d.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Fc receptor, Treatment
Abstract: E1040
Type: Eposter Presentation
Background
The Fcγ receptor IIb (FcγRIIb) is a low-affinity Fcγ receptor that negatively regulates B-cell receptor (BCR) function in normal B-cells. In chronic lymphocytic leukemia (CLL) cells, FcγRIIb may exert this inhibitory effect when colligated with the BCR. Since CLL cells are activated in vivo, the clinical impact of FcγRIIb expression in this malignancy is worth of being investigated.
Aims
The aims of this study were to: (1) analyze the basal expression of FcγRIIb on CLL cells and normal B-cells; (2) investigate the relationship between FcγRIIb and well-known prognostic markers; and (3) explore the prognostic impact of FcγRIIb on clinical outcome of patients with CLL.
Methods
The study population included 174 patients with active CLL and 34 healthy donors. The median age at diagnosis was 66 years (34-88) and follow-up was 8.0 years (0-38.7). FcγRIIb expression was determined by flow cytometry using an Alexa488-conjugated mAb specific for human FcγRIIb within the following combinations: FcγRIIb/CD38/CD19/CD5 and FcγRIIb/CD49d/CD19/CD5. Results were expressed as the ratio between the MFI for FcγRIIb and the MFI for the corresponding isotype (MFIR). The Fisher’s exact test and the Mann-Whitney U test were used for comparisons between groups. Kaplan–Meier survival and Cox regression analysis were performed to evaluate the correlation of FcγRIIb expression with clinical outcome. Best cut-offs for time to treatment (TTT) were determined by ROC curves.
Results
Both CD5+CD19+ leukemic cells and CD19+ normal B-cells expressed FcγRIIb, with no significant differences in MFIR between the populations [median MFIR: 46.4 (8.3-153.4) vs 49.4 (30.8-73.2), p=0.812]. FcγRIIb expression, however, was highly heterogeneous among CLL samples, with 4.5% showing very high expression (outliers). Within clones from the same patient, FcγRIIb MFIR was higher on CD38+ or CD49d+ cells than on CD38- or CD49d- cells, respectively (p<0.01). Eighty-one percent (142/174) of patients showed high (MFIR>30.8) and 19% had low FcγRIIb expression (MFIR<30.8). We did not find any association between FcγRIIb expression and well-known prognostic markers except CD49d (p=0.025). However, the correlation between FcγRIIb and CD49d expression was very weak (κ=0.085) showing concordance in only 39.7% of cases. At the time of analysis, 52 patients (29.9%) had required therapy. Patients with low FcγRIIb expression had a significantly shorter TTT than those with high FcγRIIb expression (median 46.07 vs 62.7 months; log-rank p<0.028). In univariate analysis, other prognostic parameters, such as clinical stage, serum B2M, elevated LDH, ZAP70, CD38 and CD49d expression, IGHV mutational status, cytogenetics, and mutations of NOTCH1 and SF3B1 significantly correlated with shorter TTT (p<0.01). In a multivariate analysis incorporating FcγRIIb expression, ZAP70, CD38 and CD49d expression, IGHV mutational status, cytogenetics, and mutations of NOTCH1 and SF3B1, only low FcγRIIb expression (HR 2.66, 95%CI 1.22-5.80, p=0.014), unmutated IGHV (HR 3.02, 95%CI 1.30-7.02, p=0.010), and mutated SF3B1 (HR 11.27, 95% CI 2.82-45.12, p=0.001) and NOTCH1 (HR 4.79, 95%CI 1.31-17.48, p=0.018) retained prognostic significance for shorter TTT.
Conclusion
FcγRIIb expression can predict time to treatment in CLL, underlying a key role of the receptor in the progression of this malignancy. These results encourage further investigation to characterize the mechanisms by which FcγRIIb controls CLL cell activation and to uncover the relationship of FcγRIIb with other molecules, particularly CD49d.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Fc receptor, Treatment
Type: Eposter Presentation
Background
The Fcγ receptor IIb (FcγRIIb) is a low-affinity Fcγ receptor that negatively regulates B-cell receptor (BCR) function in normal B-cells. In chronic lymphocytic leukemia (CLL) cells, FcγRIIb may exert this inhibitory effect when colligated with the BCR. Since CLL cells are activated in vivo, the clinical impact of FcγRIIb expression in this malignancy is worth of being investigated.
Aims
The aims of this study were to: (1) analyze the basal expression of FcγRIIb on CLL cells and normal B-cells; (2) investigate the relationship between FcγRIIb and well-known prognostic markers; and (3) explore the prognostic impact of FcγRIIb on clinical outcome of patients with CLL.
Methods
The study population included 174 patients with active CLL and 34 healthy donors. The median age at diagnosis was 66 years (34-88) and follow-up was 8.0 years (0-38.7). FcγRIIb expression was determined by flow cytometry using an Alexa488-conjugated mAb specific for human FcγRIIb within the following combinations: FcγRIIb/CD38/CD19/CD5 and FcγRIIb/CD49d/CD19/CD5. Results were expressed as the ratio between the MFI for FcγRIIb and the MFI for the corresponding isotype (MFIR). The Fisher’s exact test and the Mann-Whitney U test were used for comparisons between groups. Kaplan–Meier survival and Cox regression analysis were performed to evaluate the correlation of FcγRIIb expression with clinical outcome. Best cut-offs for time to treatment (TTT) were determined by ROC curves.
Results
Both CD5+CD19+ leukemic cells and CD19+ normal B-cells expressed FcγRIIb, with no significant differences in MFIR between the populations [median MFIR: 46.4 (8.3-153.4) vs 49.4 (30.8-73.2), p=0.812]. FcγRIIb expression, however, was highly heterogeneous among CLL samples, with 4.5% showing very high expression (outliers). Within clones from the same patient, FcγRIIb MFIR was higher on CD38+ or CD49d+ cells than on CD38- or CD49d- cells, respectively (p<0.01). Eighty-one percent (142/174) of patients showed high (MFIR>30.8) and 19% had low FcγRIIb expression (MFIR<30.8). We did not find any association between FcγRIIb expression and well-known prognostic markers except CD49d (p=0.025). However, the correlation between FcγRIIb and CD49d expression was very weak (κ=0.085) showing concordance in only 39.7% of cases. At the time of analysis, 52 patients (29.9%) had required therapy. Patients with low FcγRIIb expression had a significantly shorter TTT than those with high FcγRIIb expression (median 46.07 vs 62.7 months; log-rank p<0.028). In univariate analysis, other prognostic parameters, such as clinical stage, serum B2M, elevated LDH, ZAP70, CD38 and CD49d expression, IGHV mutational status, cytogenetics, and mutations of NOTCH1 and SF3B1 significantly correlated with shorter TTT (p<0.01). In a multivariate analysis incorporating FcγRIIb expression, ZAP70, CD38 and CD49d expression, IGHV mutational status, cytogenetics, and mutations of NOTCH1 and SF3B1, only low FcγRIIb expression (HR 2.66, 95%CI 1.22-5.80, p=0.014), unmutated IGHV (HR 3.02, 95%CI 1.30-7.02, p=0.010), and mutated SF3B1 (HR 11.27, 95% CI 2.82-45.12, p=0.001) and NOTCH1 (HR 4.79, 95%CI 1.31-17.48, p=0.018) retained prognostic significance for shorter TTT.
Conclusion
FcγRIIb expression can predict time to treatment in CLL, underlying a key role of the receptor in the progression of this malignancy. These results encourage further investigation to characterize the mechanisms by which FcγRIIb controls CLL cell activation and to uncover the relationship of FcγRIIb with other molecules, particularly CD49d.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Fc receptor, Treatment
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