Contributions
Abstract: PB1769
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is a disease characterized by the accumulation of morphologically mature monoclonal lymphocytes B with CD19+/CD5+/CD23+ phenotype in lymphoid tissue, peripheral blood and bone marrow. The course of CLL is chronic by default. Of note, however, is its heterogeneity. Programmed cell death protein 1 and its ligand 1 (PD-1, PD-L1) as well as CD200 and CD200 receptor (CD200R) are major inhibitory receptors regulating T cell exhaustion, i.e. a state of T cell dysfunction. The role of lymphocyte exhaustion in the natural history of CLL is still a matter of discussion.
Aims
The aim of this study was to determine the percentages and absolute numbers of exhausted lymphocytes B and T in peripheral blood and bone marrow of CLL patients. Moreover, we analyzed relationship between the number of PD-1-positive, PD-L1-positive, CD200-positive, and CD200R-positive lymphocytes and established prognostic factors in CLL.
Methods
The study included 60 untreated patients with CLL and 20 healthy subjects. The immunophenotype of peripheral blood mononuclear cells (in both groups) and bone marrow cells (solely in the CLL group) was determined by means of flow cytometry.
Results
Patients with CLL showed higher frequencies and absolute number of exhausted B lymphocytes CD19+PD-1+ (p<0.0001), CD19+PD-L1+ (p<0.0001), CD19+CD200+ (p<0.0001) and CD19+CD200R+ (p<0.0001), as well as higher frequencies and absolute number of exhausted T helper lymphocytes CD4+PD-1+ (p=0.0021), CD4+PD-L1+ (p=0.0032), CD4+CD200+ (p=0.0027), CD4+CD200R+ (p=0.0062), and exhaused T cytotixic lymhocytes CD8+PD-1+ (p=0.0036), CD8+PD-L1+ (p=0.0029), CD8+CD200+ (p=0.0038), CD8+CD200R+ (p=0.0073) than the controls in the peripheral blood. Similar observations were done in the bone marrow samples (p<0.0001, p<0.0001, p<0.0001, p<0.0001, p=0.0134, p=0.0183, p=0.0263, p=0.0169, p=0.0261, p=0.0362, p=0.0293, and p=0.0379, respectively). Enhanced exhaustion of peripheral blood and bone marrow lymphocytes was associated with higher Rai stage, increased concentration of lactate dehydrogenase and beta-2 microglobulin, and more rapid progression of the disease. The number of lymphocytes B CD19+ZAP-70+ correlated positively with the number of CD19+PD-1+ B cells, CD4+PD-1+ T cells, and CD8+CD200+ T cells.
Conclusion
The study confirmed the association between unfavorable prognosis and high expression of exhaustion markers in CLL patients. Determination of PD-1+, PD-L1+, CD200+ and CD200R+ lymphocytes T and B constitutes valuable diagnostic tool, completing cytometric evaluation of CLL.
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Progression, Immunophenotype, Immunity, Chronic Lymphocytic Leukemia
Abstract: PB1769
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is a disease characterized by the accumulation of morphologically mature monoclonal lymphocytes B with CD19+/CD5+/CD23+ phenotype in lymphoid tissue, peripheral blood and bone marrow. The course of CLL is chronic by default. Of note, however, is its heterogeneity. Programmed cell death protein 1 and its ligand 1 (PD-1, PD-L1) as well as CD200 and CD200 receptor (CD200R) are major inhibitory receptors regulating T cell exhaustion, i.e. a state of T cell dysfunction. The role of lymphocyte exhaustion in the natural history of CLL is still a matter of discussion.
Aims
The aim of this study was to determine the percentages and absolute numbers of exhausted lymphocytes B and T in peripheral blood and bone marrow of CLL patients. Moreover, we analyzed relationship between the number of PD-1-positive, PD-L1-positive, CD200-positive, and CD200R-positive lymphocytes and established prognostic factors in CLL.
Methods
The study included 60 untreated patients with CLL and 20 healthy subjects. The immunophenotype of peripheral blood mononuclear cells (in both groups) and bone marrow cells (solely in the CLL group) was determined by means of flow cytometry.
Results
Patients with CLL showed higher frequencies and absolute number of exhausted B lymphocytes CD19+PD-1+ (p<0.0001), CD19+PD-L1+ (p<0.0001), CD19+CD200+ (p<0.0001) and CD19+CD200R+ (p<0.0001), as well as higher frequencies and absolute number of exhausted T helper lymphocytes CD4+PD-1+ (p=0.0021), CD4+PD-L1+ (p=0.0032), CD4+CD200+ (p=0.0027), CD4+CD200R+ (p=0.0062), and exhaused T cytotixic lymhocytes CD8+PD-1+ (p=0.0036), CD8+PD-L1+ (p=0.0029), CD8+CD200+ (p=0.0038), CD8+CD200R+ (p=0.0073) than the controls in the peripheral blood. Similar observations were done in the bone marrow samples (p<0.0001, p<0.0001, p<0.0001, p<0.0001, p=0.0134, p=0.0183, p=0.0263, p=0.0169, p=0.0261, p=0.0362, p=0.0293, and p=0.0379, respectively). Enhanced exhaustion of peripheral blood and bone marrow lymphocytes was associated with higher Rai stage, increased concentration of lactate dehydrogenase and beta-2 microglobulin, and more rapid progression of the disease. The number of lymphocytes B CD19+ZAP-70+ correlated positively with the number of CD19+PD-1+ B cells, CD4+PD-1+ T cells, and CD8+CD200+ T cells.
Conclusion
The study confirmed the association between unfavorable prognosis and high expression of exhaustion markers in CLL patients. Determination of PD-1+, PD-L1+, CD200+ and CD200R+ lymphocytes T and B constitutes valuable diagnostic tool, completing cytometric evaluation of CLL.
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Progression, Immunophenotype, Immunity, Chronic Lymphocytic Leukemia