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SERUM LEVELS OF CYTOKINES AND ADHESION MOLECULES IN NEWLY DIAGNOSED B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA AND IN COMPLETE REMISSION, AND THEIR ASSOCIATION WITH OVERALL SURVIVAL
Author(s): ,
Jan M Horacek
Affiliations:
Department of Military Internal Medicine and Military Hygiene,University of Defence, Faculty of Military Health Sciences,Hradec Kralove,Czech Republic;Department of Internal Medicine IV – Hematology,University Hospital and Charles University, Faculty of Medicine,Hradec Kralove,Czech Republic
,
Tomas Kupsa
Affiliations:
Department of Military Internal Medicine and Military Hygiene,University of Defence, Faculty of Military Health Sciences,Hradec Kralove,Czech Republic;Department of Internal Medicine IV – Hematology,University Hospital and Charles University, Faculty of Medicine,Hradec Kralove,Czech Republic
,
Jan Vanek
Affiliations:
Department of Informatics and Quantitative Methods,University of Hradec Kralove, Faculty of Informatics and Management,Hradec Kralove,Czech Republic
,
Ladislav Jebavy
Affiliations:
Department of Military Internal Medicine and Military Hygiene,University of Defence, Faculty of Military Health Sciences,Hradec Kralove,Czech Republic;Department of Internal Medicine IV – Hematology,University Hospital and Charles University, Faculty of Medicine,Hradec Kralove,Czech Republic
Pavel Zak
Affiliations:
Department of Internal Medicine IV – Hematology,University Hospital and Charles University, Faculty of Medicine,Hradec Kralove,Czech Republic
(Abstract release date: 05/17/18) EHA Library. Horacek J. 06/14/18; 216187; PB1632
Prof. Dr. Jan M Horacek
Prof. Dr. Jan M Horacek
Contributions
Abstract

Abstract: PB1632

Type: Publication Only

Background
Dysregulated production of cytokines and adhesion molecules has been implicated in the onset and progression of various types of leukemia. Further knowledge gained from multiple cytokine and adhesion molecule evaluation could help to improve treatment outcomes.

Aims
The aim of this study was to evaluate serum levels of selected cytokines and adhesion molecules in newly diagnosed B-cell precursor acute lymphoblastic leukemia (B-ALL) and in complete remission, and their association with overall survival.

Methods

A total of 40 newly diagnosed B-ALL patients (median age 49, range 19–75 years, 27 males) were included in this study. Serum samples were taken at diagnosis and in complete remission. We evaluated serum levels of 12 cytokines and 5 adhesion molecules. From cytokines, we measured Interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10), Interferon-γ (IFN-γ), Tumour Necrosis Factor-α (TNF-α), Epidermal Growth Factor (EGF), Vascular Endothelial Growth Factor (VEGF) and Monocyte Chemotactic Protein-1 (MCP-1). From soluble adhesion molecules, we measured E-Selectin (E-SEL), L-Selectin (L-SEL), P-Selectin (P-SEL), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1). All analytes were measured by biochip array technology on Evidence Investigator analyzer (Randox). Correlations between analytes and overall survival were evaluated separately in both clinical situations. Statistical evaluation was done by a professional statistician using software R 3.4.3 (R Core Team 2017). Probability values (p)<0.01 were considered statistically significant.

Results

At diagnosis of B-ALL, we found significantly higher levels of IL-6, IL-8, IL-10, TNF-α, E-SEL, L-SEL, ICAM-1, VCAM-1 (p<0.01) and significantly lower levels of EGF, P-SEL (p<0.01) in comparison with complete remission. Serum levels of other evaluated analytes were without significant differences. In complete remission, EGF correlated with P-SEL (r=0.755; p<0.001) and IL-1α with IL-4 (r=0.612; p=0.007). Other correlations between analytes did not reach statistical significance. Inferior overall survival was associated with higher IL-2 level at diagnosis (r=0.448; p=0.003) and higher L-SEL levels in complete remission (r=0.410; p=0.001).

Conclusion

Conclusion: Our results show that serum levels of some cytokines and adhesion molecules are significantly altered in newly diagnosed B-ALL, reflecting activity of the disease. In our cohort of B-ALL patients, we found statistically significant correlations between inferior overall survival and higher IL-2 levels at diagnosis and higher L-SEL levels in complete remission. Better understanding of leukemia microenvironment is essential for development of new treatment approaches. Further studies in this field are warranted.

This work was supported by a long-term organization development plan 1011 (FMHS) and by program PROGRES Q40/08.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Adhesion, B cell acute lymphoblastic leukemia, Cytokine

Abstract: PB1632

Type: Publication Only

Background
Dysregulated production of cytokines and adhesion molecules has been implicated in the onset and progression of various types of leukemia. Further knowledge gained from multiple cytokine and adhesion molecule evaluation could help to improve treatment outcomes.

Aims
The aim of this study was to evaluate serum levels of selected cytokines and adhesion molecules in newly diagnosed B-cell precursor acute lymphoblastic leukemia (B-ALL) and in complete remission, and their association with overall survival.

Methods

A total of 40 newly diagnosed B-ALL patients (median age 49, range 19–75 years, 27 males) were included in this study. Serum samples were taken at diagnosis and in complete remission. We evaluated serum levels of 12 cytokines and 5 adhesion molecules. From cytokines, we measured Interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10), Interferon-γ (IFN-γ), Tumour Necrosis Factor-α (TNF-α), Epidermal Growth Factor (EGF), Vascular Endothelial Growth Factor (VEGF) and Monocyte Chemotactic Protein-1 (MCP-1). From soluble adhesion molecules, we measured E-Selectin (E-SEL), L-Selectin (L-SEL), P-Selectin (P-SEL), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1). All analytes were measured by biochip array technology on Evidence Investigator analyzer (Randox). Correlations between analytes and overall survival were evaluated separately in both clinical situations. Statistical evaluation was done by a professional statistician using software R 3.4.3 (R Core Team 2017). Probability values (p)<0.01 were considered statistically significant.

Results

At diagnosis of B-ALL, we found significantly higher levels of IL-6, IL-8, IL-10, TNF-α, E-SEL, L-SEL, ICAM-1, VCAM-1 (p<0.01) and significantly lower levels of EGF, P-SEL (p<0.01) in comparison with complete remission. Serum levels of other evaluated analytes were without significant differences. In complete remission, EGF correlated with P-SEL (r=0.755; p<0.001) and IL-1α with IL-4 (r=0.612; p=0.007). Other correlations between analytes did not reach statistical significance. Inferior overall survival was associated with higher IL-2 level at diagnosis (r=0.448; p=0.003) and higher L-SEL levels in complete remission (r=0.410; p=0.001).

Conclusion

Conclusion: Our results show that serum levels of some cytokines and adhesion molecules are significantly altered in newly diagnosed B-ALL, reflecting activity of the disease. In our cohort of B-ALL patients, we found statistically significant correlations between inferior overall survival and higher IL-2 levels at diagnosis and higher L-SEL levels in complete remission. Better understanding of leukemia microenvironment is essential for development of new treatment approaches. Further studies in this field are warranted.

This work was supported by a long-term organization development plan 1011 (FMHS) and by program PROGRES Q40/08.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Adhesion, B cell acute lymphoblastic leukemia, Cytokine

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