Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia.
Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is signific...
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doaj-9703eff2c92f44caa45af17aed231c402020-11-24T22:05:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7210710.1371/journal.pone.0072107Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia.Maria GöbelLewin EiseleMichael MöllmannAndreas HüttmannPatricia JohanssonRené ScholtysikManuela BergmannRaymonde BuschHartmut DöhnerMichael HallekTill SeilerStephan StilgenbauerLudger Klein-HitpassUlrich DührsenJan DürigProgranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38(+)ZAP-70(+) as compared to indolent CD38(-)ZAP-70(-) chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p-) as detected by flourescence in situ hybridization (FISH) and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163). Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13-3.76, p = 0.018), unmutated IGHV status (HR = 5.63, 95%-CI = 3.05-10.38, p<0.001), high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09-3.89, p = 0.026) but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA.http://europepmc.org/articles/PMC3751910?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Göbel Lewin Eisele Michael Möllmann Andreas Hüttmann Patricia Johansson René Scholtysik Manuela Bergmann Raymonde Busch Hartmut Döhner Michael Hallek Till Seiler Stephan Stilgenbauer Ludger Klein-Hitpass Ulrich Dührsen Jan Dürig |
spellingShingle |
Maria Göbel Lewin Eisele Michael Möllmann Andreas Hüttmann Patricia Johansson René Scholtysik Manuela Bergmann Raymonde Busch Hartmut Döhner Michael Hallek Till Seiler Stephan Stilgenbauer Ludger Klein-Hitpass Ulrich Dührsen Jan Dürig Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. PLoS ONE |
author_facet |
Maria Göbel Lewin Eisele Michael Möllmann Andreas Hüttmann Patricia Johansson René Scholtysik Manuela Bergmann Raymonde Busch Hartmut Döhner Michael Hallek Till Seiler Stephan Stilgenbauer Ludger Klein-Hitpass Ulrich Dührsen Jan Dürig |
author_sort |
Maria Göbel |
title |
Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. |
title_short |
Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. |
title_full |
Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. |
title_fullStr |
Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. |
title_full_unstemmed |
Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. |
title_sort |
progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38(+)ZAP-70(+) as compared to indolent CD38(-)ZAP-70(-) chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p-) as detected by flourescence in situ hybridization (FISH) and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163). Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13-3.76, p = 0.018), unmutated IGHV status (HR = 5.63, 95%-CI = 3.05-10.38, p<0.001), high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09-3.89, p = 0.026) but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA. |
url |
http://europepmc.org/articles/PMC3751910?pdf=render |
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