BMP7 expression correlates with secondary drug resistance in mantle cell lymphoma.
OBJECTIVE
We designed a gene profiling experiment to identify genes involved in secondary drug resistance in mantle cell lymphomas (MCL).


METHODS
We obtained paired tissue samples collected from the same patients before treatment and after relapse or progression. Variations in gene expression between the 2 samples were estimated for 5 patients. For each gene, the mean variation was estimated for patients with a refractory primary tumor and for responders who developed secondary drug resistance. Nine genes of interest were selected on the basis of the magnitude and statistical significance of the variation of expression in responders and non-responders.


RESULTS
BMP7 was the only one with significantly increased expression at relapse in patients who developed secondary resistance. Validation of BMP7 as a key gene involved in secondary resistance was performed using cultures of cell line. Incubation of BMP7 with MCL cell lines increased their resistance to bortezomib and cytarabine, while inhibition of BMP7 expression by siRNA correlated with increased cell death linked to drug application.


CONCLUSIONS
Variations in gene expression after treatment point out BMP7 as a key gene involved in secondary resistance in mantle cell lymphoma.
Institut de Recherche Intégrée en cancérologie à Villejuif (IRCIV), Institut de cancérologie Gustave Roussy, Villejuif, France ; Institut National de la Santé et de la Recherche Médicale (INSERM) U1009, Université Paris Sud, Institut de cancérologie Gustave Roussy, Villejuif, France.
Valérie
V
Camara-Clayette
Serge
S
Koscielny
Sébastien
S
Roux
Thierry
T
Lamy
Jacques
J
Bosq
Marc
M
Bernard
Thierry
T
Fest
Vladimir
V
Lazar
Gilbert
G
Lenoir
Vincent
V
Ribrag
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D055419:Bone Morphogenetic Protein 7 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001897:Boronic Acids / Q000494:pharmacology / Q000633:toxicity; D000069286:Bortezomib; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011719:Pyrazines / Q000494:pharmacology / Q000633:toxicity; D034622:RNA Interference; D012008:Recurrence; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D055419:Bone Morphogenetic Protein 7; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib