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CD38 AND INTERLEUKIN 6 GENE POLYMORPHISM IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA- CORRELATION WITH CLINICAL AND LABORATORY PARAMETARS
Author(s): ,
Vojin Vukovic
Affiliations:
Lymphoma center,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia
,
Darko Antic
Affiliations:
Lymphoma center,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia;Medical Faculty,University of Belgrade,Belgrade,Serbia
,
Vladan Cokic
Affiliations:
Institute for Medical Research,University of Belgrade,Belgrade,Serbia
,
Marijana Buac
Affiliations:
Institute for Medical Research,University of Belgrade,Belgrade,Serbia
,
Milos Diklic
Affiliations:
Institute for Medical Research,University of Belgrade,Belgrade,Serbia
,
Milena Todorovic- Balint
Affiliations:
Lymphoma center,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia;Medical Faculty,University of Belgrade,Belgrade,Serbia
,
Jelena Bila
Affiliations:
Lymphoma center,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia;Medical Faculty,University of Belgrade,Belgrade,Serbia
,
Bosko Andjelic
Affiliations:
Lymphoma center,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia;Medical Faculty,University of Belgrade,Belgrade,Serbia
,
Marija Dencic- Fekete
Affiliations:
Genetic Laboratory,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia
,
Vladislava Djurasinovic
Affiliations:
Lymphoma center,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia
,
Aleksandra Sretenovic
Affiliations:
Lymphoma center,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia
,
Jelena Jelicic
Affiliations:
Lymphoma center,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia
Biljana Mihaljevic
Affiliations:
Lymphoma center,Clinic for Hematology, Clinical Center of Serbia,Belgrade,Serbia;Medical Faculty,University of Belgrade,Belgrade,Serbia
(Abstract release date: 05/19/16) EHA Library. Vukovic V. 06/09/16; 134672; PB1772
Dr. Vojin Vukovic
Dr. Vojin Vukovic
Contributions
Abstract
Abstract: PB1772

Type: Publication Only

Background
CD38 receptor and interleukin 6 (IL-6) level increases proliferation and survival of chronic lymphocytic leukemia (CLL) cells and increased CD38 expression as well as IL-6 level are a negative prognostic marker CLL patients.  CD38 and IL-6  have a genetic polymorphism characterized by a C>G variation

Aims
This study was designed to examine the influence of CD38 (184C/G; rs6449182) and IL-6 (-174 G/C; rs1800795) gene polymorphism on laboratory and clinical parameters in chronic lymphocytic leukemia (CLL) patients.

Methods
Genotyping polymorphism is performed using restriction fragment length polymorphism-polymerase chain reaction for CD38 (184C/G) and IL-6 (-174 G/C) in 44 CLL patients and 5 healthy subjects. We separated CLL patients in three groups: 1) the G allele for IL-6 and C allele for CD38; 2) the C allele for IL-6 and CD38; 3) the full fragment for either IL-6 or CD38. The plasma level of VEGF was measured using immunoassay. Kaplan-Meier method was used for estimating survival rates.

Results
A higher prevalence of the C allele was found both in CD38 (184C/G, 84%) and IL-6 (-174 G/C, 66%) gene polymorphism of CLL patients. Furthermore, we found a lower level of CD38-positive cells in group 1 of CLL patients. The group 3 has significantly higher level of thrombocytes and lactate dehydrogenase (425 U/l, p<0.05) than group 2. The group 1 has increased beta 2 microglobulin in comparison of group 3. According to previous reports for a strong correlation between CD38 and VEGF expression, we found increased levels of plasma VEGF (med 50, range 16 - 438 ng/mL) in CLL patients vs. control subjects and in group 1 of CLL vs. other two groups (med 79 vs. 50 and 53 ng/mL in groups 2 and 3, respectively). According to the pattern of bone marrow infiltration, the diffuse type was the most present in group 1 (33%), while the nodular/interstitial was dominant in group 3 (91.7%). Furthermore, patients in the group 3 demonstrated the most favorable clinical stage according to Binet (A - 91.7%) and Rai (0 – 75%). Regarding CD38 expression, there was no significant difference between groups, although patients with C allele exhibited reduced CD38 expression (12% vs. 25%). Mean overall survival was 97, 101 and 82 months in group 1, 2 and 3, respectively without statistical significance. Median survival in group 1 and 3 was 65 and 79 months, respectively, while in group 2 was not reached . No statistical significant difference in survival among three groups was noted (p = 0.90).

Conclusion
Presented results revealed that CLL patients with the full fragment for either IL-6 or CD38 genes tend to have more favorable clinical and laboratory parameters at diagnosis, but do not exhibit survival advantage.

Session topic: E-poster

Keyword(s): CD38, Chronic lymphocytic leukemia, Gene polymorphism, IL-6
Abstract: PB1772

Type: Publication Only

Background
CD38 receptor and interleukin 6 (IL-6) level increases proliferation and survival of chronic lymphocytic leukemia (CLL) cells and increased CD38 expression as well as IL-6 level are a negative prognostic marker CLL patients.  CD38 and IL-6  have a genetic polymorphism characterized by a C>G variation

Aims
This study was designed to examine the influence of CD38 (184C/G; rs6449182) and IL-6 (-174 G/C; rs1800795) gene polymorphism on laboratory and clinical parameters in chronic lymphocytic leukemia (CLL) patients.

Methods
Genotyping polymorphism is performed using restriction fragment length polymorphism-polymerase chain reaction for CD38 (184C/G) and IL-6 (-174 G/C) in 44 CLL patients and 5 healthy subjects. We separated CLL patients in three groups: 1) the G allele for IL-6 and C allele for CD38; 2) the C allele for IL-6 and CD38; 3) the full fragment for either IL-6 or CD38. The plasma level of VEGF was measured using immunoassay. Kaplan-Meier method was used for estimating survival rates.

Results
A higher prevalence of the C allele was found both in CD38 (184C/G, 84%) and IL-6 (-174 G/C, 66%) gene polymorphism of CLL patients. Furthermore, we found a lower level of CD38-positive cells in group 1 of CLL patients. The group 3 has significantly higher level of thrombocytes and lactate dehydrogenase (425 U/l, p<0.05) than group 2. The group 1 has increased beta 2 microglobulin in comparison of group 3. According to previous reports for a strong correlation between CD38 and VEGF expression, we found increased levels of plasma VEGF (med 50, range 16 - 438 ng/mL) in CLL patients vs. control subjects and in group 1 of CLL vs. other two groups (med 79 vs. 50 and 53 ng/mL in groups 2 and 3, respectively). According to the pattern of bone marrow infiltration, the diffuse type was the most present in group 1 (33%), while the nodular/interstitial was dominant in group 3 (91.7%). Furthermore, patients in the group 3 demonstrated the most favorable clinical stage according to Binet (A - 91.7%) and Rai (0 – 75%). Regarding CD38 expression, there was no significant difference between groups, although patients with C allele exhibited reduced CD38 expression (12% vs. 25%). Mean overall survival was 97, 101 and 82 months in group 1, 2 and 3, respectively without statistical significance. Median survival in group 1 and 3 was 65 and 79 months, respectively, while in group 2 was not reached . No statistical significant difference in survival among three groups was noted (p = 0.90).

Conclusion
Presented results revealed that CLL patients with the full fragment for either IL-6 or CD38 genes tend to have more favorable clinical and laboratory parameters at diagnosis, but do not exhibit survival advantage.

Session topic: E-poster

Keyword(s): CD38, Chronic lymphocytic leukemia, Gene polymorphism, IL-6

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