Naslov
Bone morphogenetic proteins and receptors are over-expressed in bone marrow samples of multiple myeloma patients and support myeloma cells by inducing ID genes

Autori
Grčević, Danka ; Kušec, Rajko ; Kovačić, Nataša ; Lukić, Anita ; Lukić, Ivan Krešimir ; Ivčević, Sanja ; Nemet, Damir ; Kolonić Ostojić, Slobodanka ; Serventi Seiwerth, Ranka ; Croucher, Peter I. ; Marušić, Ana

Izvornik
Leukemia research (0145-2126) 34 (2010), 6; 742-751

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
bone morphogenetic proteins ; multiple myeloma ; gene expression

Sažetak
To assess the role of bone morphogenetic proteins (BMPs) in the pathogenesis of multiple myeloma (MM), we investigated the expression of BMPs, their receptors and intracellular molecules targeted by BMP signal in MM bone- marrow (BM) samples. BM cells from MM patients (n=32) significantly over-expressed BMP4, BMP6, ALK2 and ACTR2A, paralleled by decreased expression of the BMP antagonist NOG, compared with control BM samples (n=15). ROC curve analysis revealed the clinical usefulness of the gene expression values for BMP4, BMP6, ALK2, ACTR2A and NOG as MM diagnostic markers, with BMP6 having the highest sensitivity and specificity. Within MM BM cells, the source of BMPs was mainly CD138+ population and the expression of BMP6 and ALK2 significantly correlated with the percentage of plasma-cells. Since primary myeloma cells poorly survive in culture, we tested BMP effect on myeloma cell lines NCI H929 and Thiel. BMPs induced ID1, ID2 and IL-6, and suppressed p21 and BAX gene expression, and also suppressed bax protein expression, mostly in Thiel cells. Taken collectively, our results indicate that BMPs may be the autocrine factors that promote myeloma cell survival by inducing ID family of oncogenes and increasing the ratio between the expression of pro-survival and pro-apoptotic molecules.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA