COMPLEX ACTIVATION OF ANGIOGENIC SIGNALING IN CHRONIC LYMPHOCYTIC LEUKEMIA: EVIDENCE FROM CIRCULATING ANGIOGENIC CYTOKINES

Konference: 2014 19th Congress of the European Hematology Association - účast ČR

Kategorie: Maligní lymfomy a leukémie

Téma: Chronic lymphocytic leukemia and related disorders - Biology (Poster)

Číslo abstraktu: P212

Autoři: MUDr. Lukáš Smolej, Ph.D.; Doc.RNDr. Ctirad Andrýs, Ph.D.; Mgr. Vladimíra Řezáčová, Ph.D.; MUDr. Martin Šimkovič; MUDr. Monika Motyčková; MUDr. David Belada, Ph.D.; Prof. MUDr. Pavel Žák, Ph.D.

ABSSUB-5690

Background: Chronic lymphocytic leukemia (CLL) has a remarkably heterogeneous clinical course. Assessment of angiogenesis may potentially improve individual patient´s prognostic stratification.

Aims: To investigate prognostic relevance of circulating basic fibroblast growth factor (FGF-2), vascular endothelial growth factor (VEGF), soluble endoglin (sCD105), endostatin, and angiopoietin-2 (Ang-2) in patients with CLL.

Methods: Plasma levels of angiogenic factors were quantified  using enzyme-linked immunosorbent assay in patients with untreated CLL (median age, 63 years [range, 31-88]; males, 69 %) (FGF-2, VEGF, n=181; sCD105, n=175; endostatin, n=137; Ang-2, n=130). Eighty healthy donors served as control group.

Results: All circulating cytokines except endostatin were significantly elevated in CLL patients vs. controls (FGF-2 and sCD105: p<0.0001; VEGF, p=0.0004; Ang-2: p=0.001). sCD105 progressively increased with advancing Rai stages (Rai low vs. intermediate vs. high, p=0.024 and p=0.033). Patients with progressive disease had significantly higher levels of sCD105, endostatin and Ang-2 in comparison to patients with stable course (sCD105: p=0.0008; endostatin: p=0.019; Ang-2: p=0.015). Time to treatment was significantly shorter in patients with high sCD105 levels (median 15 months vs. not reached, p=0.0045). In patients who achieved at least partial response after fludarabine-based chemo(immuno)therapy, levels of FGF-2, VEGF, and sCD105 decreased significantly (p<0.0001, p=0.0027 and p=0.0098).

Summary/Conclusion: Our results indicate that a complex network of angiogenic signaling is active in CLL and has an impact on clinical course; sCD105 appears to have the best prognostic value among these cytokines. Updated results will be presented. Supported by grant NT/13412-4 from the Internal Grant Agency, Ministry of Health, Czech Republic, by DRO (Univ Hospital Hradec Králové, 00179906) from Ministry of Health, Czech Republic, and by programme PRVOUK P37/08.

Keywords: Angiogenesis, Chronic lymphocytic leukemia, Microenvironment

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Datum přednesení příspěvku: 13. 6. 2014