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IGF-1R is overexpressed in poor-prognostic subtypes of multiple myeloma

Leukemia volume 20, pages 174–176 (2006)Cite this article

Insulin growth factor-1 (IGF-1) is an important survival and growth factor in multiple myeloma (MM)1 and various other malignancies,2 and its receptor (IGF-1R) has been recently shown to be an ideal therapeutic target.3 Few studies have examined IGF-1R and IGF-1 expression in MM patients. To better understand the distribution of the receptor in myeloma, we decided to perform a detailed study of its expression using gene expression profiling.

We investigated the mRNA expression of IGF-1 and IGF-1R in normal and malignant plasma cells (PC) as part of gene expression profiling studies in PC from 15 normal individuals and 147 patients with various PC neoplasm (22 monoclonal gammopathy of undetermined significance (MGUS), 24 smoldering MM (SMM) and 101 symptomatic MM). Of the 101 MM cases, 72 were newly diagnosed and 29 were relapsed cases. The samples were all collected under informed consent and the study was approved by the Mayo Clinic Institutional Review Board. Bone marrow aspirates were enriched for PCs using CD138+ immunomagnetic bead selection. Total RNA was extracted, converted to biotinylated cRNA and hybridized to U133A gene chips (Affymetrix, Santa Clara, CA, USA). Gene expression intensity values were log transformed, normalized to the median and analyzed using GeneSpring 7 (Silicon Genetics, Redwood City, CA, USA). Patients were then classified according to expression of seven genes (FGFR3, MMSET, ITGB7, MAF, CCND3, CCND1 and CCND2) as previously described.4 This gene expression-based molecular classification (TC classification) accurately identifies all the major cytogenetic categories in MM: t(4;14)(p16;q32) (based on FGFR3/MMSET expression); t(14;16)(q32;q23) and t(14;20) (based on expression of ITGB7 and MAF); t(6;14) assessed by high level of CCND3 expression; t(11;14)(q13;q32) based on high level of CCND1 expression; hyperdiploid MM based of aberrant low level of CCND1 expression or low D1 with high D2 expression (D1+D2 group). Two other TC groups, high CCND2 but no CCND1 expression (D2 group) or no CCND1 or 2 expression (none group), are biologically ill-defined. Fluorescent in situ hybridization (FISH) analysis for 13q deletion (Δ13) and IgH translocations was also performed as previously described.5 Nonparametric tests were used for statistical analysis. For comparison of gene expression level between multiple groups, the Kruskal–Wallis test is used with Dunn's multiple testing correction for pair-wise comparisons. For comparison between two groups, the Mann–Whitney U-test is used. The distribution for overall survival (OS) was estimated using the method of Kaplan and Meier. The log-rank test was used to test for differences in survival between groups. OS was calculated from day of sampling to death. P-values of <0.05 is considered significant.

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Acknowledgements

R Fonseca is a Clinical Investigator of the Damon Runyon Cancer Research Fund. This work is supported by Pfizer Inc., and Grants R01 CA83724-01, SPORE P50 CA100707-01and P01 CA62242 from the National Cancer Institute. WJ Chng is funded by an International Fellowship from the Agency for Science, Technology and Research (A*STAR), Singapore.

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  1. Division of Hematology-Oncology, Mayo Clinic Scottsdale, Scottsdale, AZ, USA

    W J Chng & R Fonseca

  2. Pfizer Global Research and Development, New London, CT, USA

    A Gualberto

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  1. W J Chng
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Correspondence to R Fonseca.

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Chng, W., Gualberto, A. & Fonseca, R. IGF-1R is overexpressed in poor-prognostic subtypes of multiple myeloma. Leukemia 20, 174–176 (2006). https://doi.org/10.1038/sj.leu.2403997

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