title: Increased copy number of the interleukin-6 receptor gene is associated with adverse survival in multiple myeloma patients treated with autologous stem cell transplantation.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Min
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Park
authors.forename: Bora
authors.initials: B
authors.lastname: Oh
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Kim
authors.forename: Cha Ja
authors.initials: CJ
authors.lastname: She
authors.forename: Sang Mee
authors.initials: SM
authors.lastname: Hwang
authors.forename: Miyoung
authors.initials: M
authors.lastname: Kim
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Seonyang
authors.initials: S
authors.lastname: Park
authors.forename: Byoung Kook
authors.initials: BK
authors.lastname: Kim
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000032:analysis; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000032:analysis; D017404:In Situ Hybridization, Fluorescence; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D015999:Multivariate Analysis; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D014182:Transplantation, Autologous
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D015850:Interleukin-6; D019947:Receptors, Interleukin-6