PMID- 21220034 OWN - NLM STAT- MEDLINE DCOM- 20110913 LR - 20151119 IS - 1523-6536 (Electronic) IS - 1083-8791 (Linking) VI - 17 IP - 6 DP - 2011 Jun TI - Increased copy number of the interleukin-6 receptor gene is associated with adverse survival in multiple myeloma patients treated with autologous stem cell transplantation. PG - 810-20 LID - 10.1016/j.bbmt.2011.01.002 [doi] AB - Interleukin-6 (IL-6) is a potent pleiotropic cytokine that regulates plasma cell (PC) growth via the IL-6 receptor (IL-6R). We hypothesized that up-regulation of IL-6R in myeloma cells might confer the growth privilege to myeloma cells over bone marrow (BM) hematopoietic cells. We investigated the frequency and prognostic implication of increased copy number of the IL-6R gene by fluorescence in situ hybridization (FISH) in patients with newly diagnosed multiple myeloma (MM). One hundred two patients with newly diagnosed MM were enrolled. The FISH study for IL-6R was performed using a homemade bacterial artificial chromosome (BAC) probe for IL6R at chromosome 1q21. FISH signals were counted among BM plasma cells sorted by cytoplasmic immunoglobulin light chain staining (cIg FISH). The amplification of IL-6R was detected in 53/102 patients (52.0%). The 5-year overall survival (OS) rate of patients with IL-6R gene amplification was 41.3% versus 44.8% for those with a normal IL-6R (P = .425). In 44 patients treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT), patients with >/=3.1 copy numbers of IL-6R per PC showed adverse 5-year OS compared to those with <2.1 copies of IL-6R gene (44.4% versus 78.0%, P = .024). In multivariate analysis, the increase of IL-6R copy numbers (mean copy/PC >/=3.1) could be considered as an independent prognostic factor for MM patients who underwent ASCT. The gain of the IL-6R gene was frequent in myeloma, showing an association with adverse prognosis in myeloma patients treated with ASCT. These findings suggest the potential role of IL-6R in myeloma cell growth and therapeutic implications of the IL-6R blocker in the future. CI - Copyright (c) 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. FAU - Kim, Seon Young AU - Kim SY AD - Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea. FAU - Min, Hyun Jung AU - Min HJ FAU - Park, Hyun Kyung AU - Park HK FAU - Oh, Bora AU - Oh B FAU - Kim, Tae Young AU - Kim TY FAU - She, Cha Ja AU - She CJ FAU - Hwang, Sang Mee AU - Hwang SM FAU - Kim, Miyoung AU - Kim M FAU - Kim, Hyun Kyung AU - Kim HK FAU - Kim, Inho AU - Kim I FAU - Yoon, Sung-Soo AU - Yoon SS FAU - Park, Seonyang AU - Park S FAU - Kim, Byoung Kook AU - Kim BK FAU - Lee, Jae Hoon AU - Lee JH FAU - Lee, Dong Soon AU - Lee DS CN - Korea Multiple Myeloma Working Party LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110108 PL - United States TA - Biol Blood Marrow Transplant JT - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JID - 9600628 RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers) RN - 0 (Immunoglobulin Light Chains) RN - 0 (Interleukin-6) RN - 0 (Receptors, Interleukin-6) SB - IM MH - Aged MH - Antineoplastic Agents/administration & dosage MH - Biomarkers/analysis MH - Chromosomes, Human, Pair 1/genetics MH - Female MH - *Gene Dosage MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - Immunoglobulin Light Chains/analysis MH - In Situ Hybridization, Fluorescence MH - Interleukin-6/metabolism MH - Male MH - Multiple Myeloma/*genetics/*mortality/pathology/*therapy MH - Multivariate Analysis MH - Plasma Cells/*metabolism/pathology MH - Prognosis MH - *Receptors, Interleukin-6/genetics/metabolism MH - Survival Rate MH - Transplantation, Autologous EDAT- 2011/01/12 06:00 MHDA- 2011/09/14 06:00 CRDT- 2011/01/12 06:00 PHST- 2010/09/08 00:00 [received] PHST- 2011/01/03 00:00 [accepted] PHST- 2011/01/12 06:00 [entrez] PHST- 2011/01/12 06:00 [pubmed] PHST- 2011/09/14 06:00 [medline] AID - S1083-8791(11)00005-X [pii] AID - 10.1016/j.bbmt.2011.01.002 [doi] PST - ppublish SO - Biol Blood Marrow Transplant. 2011 Jun;17(6):810-20. doi: 10.1016/j.bbmt.2011.01.002. Epub 2011 Jan 8.