Τίτλος:
Circulating Soluble Receptor Activator of Nuclear Factor Kappa B Ligand
and C-C Motif Ligand 3 Correlate With Survival in Patients With
Waldenstrom Macroglobulinemia
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
We reviewed 55 patients with untreated symptomatic Waldenstrom
macroglobulinemia (WM) and prospectively evaluated their serum cytokines
and biological markers. High circulating chemokine (C-C) motif ligand 3
(CCL-3) serum levels predicted shorter progression-free survival while
high serum receptor activator of nuclear factor kB ligand levels
predicted shorter overall survival. This correlation reveals the
importance of these cytokines in disease biology and highlights the
significance of the interactions between WM and stromal cells for the
development of WM.
Background: Serum receptor activator of nuclear factor kB ligand
(sRANKL) and chemokine (C-C) motif ligand 3 (CCL-3) have been reported
to be elevated in Waldenstrom macroglobulinemia (WM) patients. However,
there are no published data regarding the prognostic value of these
molecules in WM regarding progression-free and overall survival.
Methods: To evaluate the effect of these markers of bone remodeling on
survival parameters, we prospectively evaluated serum cytokines and
biological markers in 55 patients with symptomatic WM before they
received any kind of treatment. Serum levels of CCL-3 and bone
remodeling markers were also evaluated in asymptomatic WM and IgM
monoclonal gammopathy of undetermined significance. Furthermore, we
assessed bone marrow biopsy samples from newly diagnosed WM patients for
CCL-3 and RANKL expression. Results: High circulating sRANKL values
predicted shorter median overall survival (46 months vs. not reached, P
= .025). High serum levels of CCL-3 predicted shorter median
progression-free survival (27 months vs. not reached, P = .048). At bone
marrow biopsy evaluation, the whole number of the neoplastic cells
revealed strong cytoplasmic positivity for CCL-3, while the neoplastic
clone did not express RANKL. Conclusion: We conclude that WM cells
produce CCL-3 and possibly enhance the production of RANKL in the bone
microenvironment. The correlation of sRANKL and CCL-3 with survival
reveals the importance of these cytokines in disease biology and
highlights the significance of the interactions between WM and stromal
cells for the development of WM. Finally, these findings provide the
rationale for the use of anti-RANKL and anti-CCL-3 drugs in animal
models of WM before their clinical evaluation.
Συγγραφείς:
Eleutherakis-Papaiakovou, Evangelos
Kastritis, Efstathios and
Gavriatopoulou, Maria
Christoulas, Dimitrios
Roussou, Maria and
Ntanasis-Stathopoulos, Ioannis
Kanellias, Nikolaos and
Papatheodorou, Athanasios
Dimopoulos, Meletios A.
Terpos,
Evangelos
Περιοδικό:
Clinical Lymphoma Myeloma & Leukemia
Εκδότης:
CIG MEDIA GROUP, LP
Λέξεις-κλειδιά:
CCL-3; Disease biology; Macroglobulinemia; RANKL; Survival
DOI:
10.1016/j.clml.2018.03.010
