Detection and follow-up of fibroblast growth factor receptor 3 expression on bone marrow and circulating plasma cells by flow cytometry in patients with t(4;14) multiple myeloma.
The t(4;14)(p16;q32) translocation, found in 15% of multiple myeloma (MM) cases, indicates a poor prognosis. Plasma cells (PC) with t(4;14) ectopically express the fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase receptor, which has potential transforming activity and may represent a therapeutic target. To detect FGFR3 protein expression, bone marrow (BM) aspirate from 200 consecutive newly diagnosed (n = 116) or relapsing (n = 74) MM patients was studied by flow cytometry (FC) using anti-CD138 and anti-FGFR3 antibodies. FC data was compared to real time quantitative-polymerase chain reaction (RQ-PCR) of the IGH-MMSET and FGFR3 transcripts. An IGH-MMSET transcript was found in 24/200 patients (12%). In 20 of these, FC detected CD138(+)/FGFR3(+) cells. No expression of FGFR3 was detected in the 4 FGFR3(-) cases by RQ-PCR. FGFR3 was never expressed on PC without t(4;14). Circulating PC (CPC) were detected in patients with (11/11) and patients without (13/41) t(4;14). In 2/8 t(4;14) cases studied longitudinally, coexisting FGFR3(+) and FGFR3(-) CPC were observed. Fluorescent in situ hybridisation (FISH) analysis of the FGFR3(-) subclones showed deletion of the der(14) in one patient. In conclusion, as a supplemental method to RQ-PCR or FISH, FC analysis of FGFR3 expression is a reliable and routinely available method for the detection and management of new therapeutic approaches of t(4;14) MM.
Chandesris
M O
MO
EA 3963, Paris VII University, Saint-Louis Hospital, AP-HP, Paris, France.
Soulier
J
J
Labaume
S
S
Crinquette
A
A
Repellini
L
L
Chemin
K
K
Malphettes
M
M
Fieschi
C
C
Asli
B
B
Uzunhan
Y
Y
Fermand
J P
JP
Bories
J C
JC
Arnulf
B
B
D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism; D010950:Plasma Cells / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000097:blood / Q000378:metabolism*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D051498:Receptor, Fibroblast Growth Factor, Type 3