Osteopontin is a prognostic factor for survival of acute myeloid leukemia patients
Menée sur 386 patients atteints d'une leucémie myéloïde aiguë nouvellement diagnostiquée, cette étude montre que les niveaux d'expression de l'ostéopontine (une protéine d'adhérence du tissu osseux) dans le sérum et les cellules blastiques de la moelle osseuse sont associés à la survie des patients
Osteopontin (OPN) is a glycoprotein that is secreted by osteoblasts and hematopoietic cells. OPN suppresses the proliferation of hematopoietic stem-cells (HSC) in vitro and may regulate the HSC-pool. Increased serum OPN-concentrations occur in chronic myeloid leukemia, multiple myeloma and acute myeloid leukemia (AML). This investigation analyzed the prognostic impact of OPN in AML. We investigated expression and relevance of OPN in newly diagnosed AML-patients from two large study-groups (AMLCG,HOVON) by immunohistochemistry (IH;n=84), enzyme-linked immunoassays (ELISA) of blood/bone-marrow sera (n=41) and on the mRNA-level by analyzing microarray-data (n=261). Expression of OPN-protein was increased in AML-patients both in bone-marrow blasts (IH) and in bone-marrow serum (ELISA) compared to healthy controls. Patients expressing high levels of OPN within the bone-marrow (IH) experienced shortened overall survival (OS,p=0.025). Multivariate analysis identified karyotype, blast-clearance (day16) and the level of OPN-expression as independent prognostic factors for OS. This prompted us to analyse microarray data from 261 patients of a third patient cohort. The analysis confirmed OPN as a prognostic marker. In detail, high OPN mRNA-expression indicated decreased event-free survival (p=0.0002) and OS (p=0.001). The prognostic role of OPN was most prominent in intermediate-risk AML. These data provide evidence that OPN-expression is an independent prognostic factor in AML.
Blood , résumé, 2012