Clinical and prognostic role of annexin A2 in multiple myeloma.
Annexin A2 (ANXA2) promotes myeloma cell growth, reduces apoptosis in myeloma cell lines, and increases osteoclast formation. ANXA2 has been described in small cohorts of samples as expressed by myeloma cells and cells of the BM microenvironment. To investigate its clinical role, we assessed 1148 samples including independent cohorts of 332 and 701 CD138-purified myeloma cell samples from previously untreated patients together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores, along with expression of ANXA2 in whole BM samples, stromal cells, osteoblasts, osteoclasts, and BM sera. ANXA2 is expressed in all normal and malignant plasma cell samples. Higher ANXA2 expression in myeloma cells is associated with significantly inferior event-free and overall survival independently of conventional prognostic factors and is associated with gene expression-determined high risk and high proliferation. Within the BM, all cell populations, including osteoblasts, osteoclasts, and stromal cells, express ANXA2. ANXA2 expression is increased significantly in myelomatous versus normal BM serum. ANXA2 exemplifies an interesting class of targetable bone-remodeling factors expressed by normal and malignant plasma cells and the BM microenvironment that have a significant impact on survival of myeloma patients.
Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany.
Anja
A
Seckinger
Tobias
T
Meissner
Jérôme
J
Moreaux
Daniela
D
Depeweg
Jens
J
Hillengass
Katja
K
Hose
Thierry
T
Rème
Angela
A
Rösen-Wolff
Anna
A
Jauch
Reinhard
R
Schnettler
Volker
V
Ewerbeck
Hartmut
H
Goldschmidt
Bernard
B
Klein
Dirk
D
Hose
D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001847:Bone Diseases / Q000175:diagnosis / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000235:genetics; D054928:Validation Studies as Topic
C472822:ANXA2 protein, human; D017306:Annexin A2; D014408:Biomarkers, Tumor; D018000:Receptors, Peptide; C514873:annexin II receptor, human