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THE ROLE OF TUMOR NECROSIS FACTOR (TNF) AND IT?S SOLUBLE RECEPTORS, STNFRI AND STNFRII, IN MYELOSUPRESSION DEVELOPING IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA (B-CLL)
Author(s): ,
Vira Barilka
Affiliations:
Immunocytology and genetics of blood neoplasms,SI Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine,Lviv,Ukraine
,
Volodymyr Matlan *
Affiliations:
* Lviv National Medical University named Danylo Halytsky, Lviv, Ukraine,Lviv,Ukraine
,
Sophiia Prymak
Affiliations:
SI Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine,Lviv,Ukraine
,
Olga Vygovska
Affiliations:
department of hematology,SI Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine,Lviv,Ukraine
,
Olga Shalay
Affiliations:
immunocytology and genetics of blood neoplasms,SI “Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine”, Lviv, Ukraine,Lviv,Ukraine
Volodymyr Loginsky
Affiliations:
immunocytology and genetics of neoplasms of blood,SI “Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine”, Lviv, Ukraine,Lviv,Ukraine
(Abstract release date: 05/19/16) EHA Library. Barilka V. 06/09/16; 134677; PB1777
Mrs. Vira Barilka
Mrs. Vira Barilka
Contributions
Abstract
Abstract: PB1777

Type: Publication Only

Background
Myelosupression with severe anemia or thrombocytopenia refers to the adverse factors in clinical course of B-CLL.  The production of TNF, a pleiotropic cytokine, and it's soluble receprors (sTNFRs), sTNFRI and sTNFRII, in B-CLL patients (pts) in blood are broken, but the final role of these proteins in development of myelosupression in B-CLL pts is studied poorly. 

Aims
To determine the role of TNF, sTNFRs in myelosupression developing in B-CLL pts.

Methods
Determination of TNF, sTNFRs was performed using blood plasma of 74 pts with B-CLL at different stages of the disease before treatment. Determining the concentration of TNF was carried out by biological methods, using mouse fibroblasts cell culture line L929. The level of sTNFRI and sTNFRII was performed by immunological methods using the kits of BioSource Europe S.A., Belgium. These parameters were analyzed in relation with complete blod counts of the pts with B-CLL. The control group consisted of 15 healthy donors. Probability statistics was evalueted using Student's t-test. The reletionship between the concentration of TNF, sTNFRs and hemograms of pts at different stages (A,B,C by Binet) of B-CLL was established by correlation coefficient (r), which was calculated by Excel program.

Results
The significantly higher levels of TNF (0,938±0,124 ng/ml), sTNFRI (2,740±0,277 ng/ml) and sTNFRII (32,180±4,350 ng/ml) were established in plasma of B-CLL pts at all stages of the disease compared with healthy donors (0,089±0,017 ng/ml; 1,210±0,014 and 4,170±0,231 ng/ml, accordingly). On the other hand, appreciably lower levels (p<0,001) of TNF (0,482±0,184 ng/ml) and sTNFRII (17,080±1,294 ng/ml) were determined in plasma of B-CLL pts at early stages in comparision with more advanced stages, B-C (1,011±0,260 and 33,300±5,690 ng/ml, accordingly). An increased reticulocytosis (>10 0/00), as a sign of hemolytic syndrome, was accompanied by significantly higher levels of TNF in plasma comparing to pts with a normal number of reticulocytes (1,266±0,114 vs 0,752±0,188 ng/ml). The concentrations of TNF and sTNFRII correlated negatively with hemoglobin level (r= - 0,37) but positively with absolute lymphocytic count (r= 0,42) at early stages of the disease. In addition, any changes in concentrations of these proteins were not detected  in plasma of B-CLL pts with thrombocytopenia.

Conclusion
These studies suggest that increasing of the concentration of TNF and sTNFRs in B-CLL, possibly as a result of their production by leukemic cells, may adversely affect hematopoiesis, promote hemolysis and development of anemia of different origin in B-CLL pts. In advanced stages of B-CLL an augmented secretion both of TNF and sTNFRII comparing with early stages may contribute to the leukemic progression. Determination of TNF and sTNFRs in blood of B-CLL pts may be used to predict the development of anemia as well as to initiate treatment, especially at early stages of this disease. 

Session topic: E-poster

Keyword(s): B-CLL, Myelosuppression, Tumor necrosis factor (TNF)
Abstract: PB1777

Type: Publication Only

Background
Myelosupression with severe anemia or thrombocytopenia refers to the adverse factors in clinical course of B-CLL.  The production of TNF, a pleiotropic cytokine, and it's soluble receprors (sTNFRs), sTNFRI and sTNFRII, in B-CLL patients (pts) in blood are broken, but the final role of these proteins in development of myelosupression in B-CLL pts is studied poorly. 

Aims
To determine the role of TNF, sTNFRs in myelosupression developing in B-CLL pts.

Methods
Determination of TNF, sTNFRs was performed using blood plasma of 74 pts with B-CLL at different stages of the disease before treatment. Determining the concentration of TNF was carried out by biological methods, using mouse fibroblasts cell culture line L929. The level of sTNFRI and sTNFRII was performed by immunological methods using the kits of BioSource Europe S.A., Belgium. These parameters were analyzed in relation with complete blod counts of the pts with B-CLL. The control group consisted of 15 healthy donors. Probability statistics was evalueted using Student's t-test. The reletionship between the concentration of TNF, sTNFRs and hemograms of pts at different stages (A,B,C by Binet) of B-CLL was established by correlation coefficient (r), which was calculated by Excel program.

Results
The significantly higher levels of TNF (0,938±0,124 ng/ml), sTNFRI (2,740±0,277 ng/ml) and sTNFRII (32,180±4,350 ng/ml) were established in plasma of B-CLL pts at all stages of the disease compared with healthy donors (0,089±0,017 ng/ml; 1,210±0,014 and 4,170±0,231 ng/ml, accordingly). On the other hand, appreciably lower levels (p<0,001) of TNF (0,482±0,184 ng/ml) and sTNFRII (17,080±1,294 ng/ml) were determined in plasma of B-CLL pts at early stages in comparision with more advanced stages, B-C (1,011±0,260 and 33,300±5,690 ng/ml, accordingly). An increased reticulocytosis (>10 0/00), as a sign of hemolytic syndrome, was accompanied by significantly higher levels of TNF in plasma comparing to pts with a normal number of reticulocytes (1,266±0,114 vs 0,752±0,188 ng/ml). The concentrations of TNF and sTNFRII correlated negatively with hemoglobin level (r= - 0,37) but positively with absolute lymphocytic count (r= 0,42) at early stages of the disease. In addition, any changes in concentrations of these proteins were not detected  in plasma of B-CLL pts with thrombocytopenia.

Conclusion
These studies suggest that increasing of the concentration of TNF and sTNFRs in B-CLL, possibly as a result of their production by leukemic cells, may adversely affect hematopoiesis, promote hemolysis and development of anemia of different origin in B-CLL pts. In advanced stages of B-CLL an augmented secretion both of TNF and sTNFRII comparing with early stages may contribute to the leukemic progression. Determination of TNF and sTNFRs in blood of B-CLL pts may be used to predict the development of anemia as well as to initiate treatment, especially at early stages of this disease. 

Session topic: E-poster

Keyword(s): B-CLL, Myelosuppression, Tumor necrosis factor (TNF)

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