Expression of Osteopontin in the Bone Marrow of Patients with Acute Myeloid Leukemia.

Osteopontin (OPN) is a secreted glycoprotein that is widely expressed in various kinds of cells and is involved in normal tissue remodelling processes as well as in certain diseases such as tumorigenesis and tumor metastasis. In the bone marrow (BM) OPN is predominantly secreted by osteoblasts and hematopoietic cells, which have been shown recently to express the OPN-binding integrins alpha4beta1 and alpha9beta1. In addition, OPN has been defined as an important factor for hematopoietic stem cells (HSCs). OPN suppressed the proliferation of HSCs in vitro and may regulate the hematopoietic stem cell pool. Increased serum OPN concentrations have been reported in chronic myeloid leukemia (CML), multiple myeloma (MM) and acute myeloid leukemia (AML).

We investigated the expression of OPN in newly diagnosed AML patients by immunohistochemistry (n=84), enzyme-linked immunoassays (ELISA) of blood /bone marrow sera (n=40) and on the RNA level by analyzing microarray data (n=261).

Expression of OPN was increased in AML patients bone marrow sera (ELISA) as well as in bone marrow blasts (IHC) Patients expressing high levels of OPN within the bone marrow (IHC: > 10 arbitrary units [AU]; ELISA: > 10 ng/ml) had significantly shorter overall survival (OS) than those with lower OPN levels. In contrast, blood OPN levels showed no predictive value. There was no correlation found between OPN expression and FAB-subtypes M0 to M7 or different karyotypes. Multivariate analysis identified the already known risk factors karyotype, blast clearance (day 16) and the level of OPN expression as independent prognostic factors for OS. Furthermore, analyses of microarray data from 261 patients of a different cohort confirmed OPN as a prognostic marker. In detail, high OPN expression demonstrated a negative predictive value for EFS and OS. Subgroup analysis revealed a significant difference in EFS and OS for OPN levels above the median in FLT3-ITD/TKD mutation negative leukemias, only. No difference was found in FLT3-mutated leukemias or in patients with favorable cytogenetics such as t(8/21) or inv (16).

These data provide evidence for OPN as prognostic marker in AML. OPN might be of pathogenetic relevance in AML. Although the mechanism is not yet understood modulation of the OPN axis might be a promising approach to improve the outcome of AML patients in the future.

No relevant conflicts of interest to declare.