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

• Published in: British journal of haematology 2007-02, Vol.136 (4), p.609-614
• Main Authors: Chandesris, M. O., Soulier, J., Labaume, S., Crinquette, A., Repellini, L., Chemin, K., Malphettes, M., Fieschi, C., Asli, B., Uzunhan, Y., Fermand, J. P., Bories, J. C., Arnulf, B.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarkers, Tumor - blood; Biomarkers, Tumor - metabolism; Bone Marrow Cells - metabolism; Chromosomes, Human, Pair 14 - genetics; Chromosomes, Human, Pair 4 - genetics; circulating plasma cells; Female; fibroblast growth factor receptor 3 detection; flow cytometry; Flow Cytometry - methods; Follow-Up Studies; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life Sciences; Male; Medical sciences; Middle Aged; multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; Multiple Myeloma - therapy; Neoplasm Proteins - blood; Neoplasm Proteins - metabolism; Plasma Cells - metabolism; Polymerase Chain Reaction - methods; Receptor, Fibroblast Growth Factor, Type 3 - blood; Receptor, Fibroblast Growth Factor, Type 3 - metabolism; t(4; 14) translocation; Translocation, Genetic; Tumor Cells, Cultured
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2006.06479.x

Summary 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.