title: Heterogeneous chromosome 12p deletion is an independent adverse prognostic factor and resistant to bortezomib-based therapy in multiple myeloma.
abstract: The deletion of 12p (del(12p)) has been described as a novel negative prognostic marker in multiple myeloma (MM) and has gained increasing attention in recent years. However, its impact on MM is still controversial. In this study, we comprehensively evaluated the clinical impact of 12p13 deletion using fluorescence in situ hybridization (FISH) on 275 newly diagnosed MM cases treated in a prospective, non-randomized clinical trial (BDH 2008/02). The results showed that deletion of 12p13 was detected in 10.5% of newly diagnosed cases and associated with multiple indicators for high tumor burden including ISS III, BM plasmacytosis larger than 50%, and renal lesion. Moreover, the cases with 12p13 deletion typically had higher incidence of del(17p), IGH translocation and t(4;14). Patients with del(12p) conferred significantly adverse prognosis for PFS and OS, even in patients subjected to bortezomib-based therapy. When adjusted to the established prognostic variables including del(13q), del(17p), t(4;14), amp(1q21), ISS stage and LDH, del(12p13) remained the powerful independent adverse factor for PFS (P = 0.007) and OS (P = 0.032). In addition, del(12p13) combined with high β2-MG, high LDH and bone lesion can further identify subpopulations with high-risk features. Our results strongly supported that del(12p13) can be used as a valuable prognostic marker in MM.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.|Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Science and Education, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Deng
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Sui
authors.affiliation: Tumor Center, The First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Dehui
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Ru
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.|Umbilical Cord Blood Bank of Tianjin, Tianjin 300020, China.
authors.forename: Lugui
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D000069286:Bortezomib / Q000494:pharmacology / Q000627:therapeutic use*; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000648:ultrastructure; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D010014:Osteolysis / Q000209:etiology; D010265:Paraproteinemias / Q000235:genetics; D011379:Prognosis; D011446:Prospective Studies; D061988:Proteasome Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D014178:Translocation, Genetic; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D061988:Proteasome Inhibitors; D000069286:Bortezomib
keywords: 12p13 deletion; CD27 gene; bortezomib; multiple myeloma; prognosis
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