title: The impact of clone size on the prognostic value of chromosome aberrations by fluorescence in situ hybridization in multiple myeloma.
abstract: OBJECTIVE
  Accumulating evidence indicates that intratumor heterogeneity is prevalent in multiple myeloma and that a collection of multiple, genetically distinct subclones are present within the myeloma cell population. It is not clear whether the size of clonal myeloma populations harboring unique cytogenetic abnormalities carry any additional prognostic value.
  
  
  METHODS
  We analyzed the prognostic impact of cytogenetic aberrations by fluorescence in situ hybridization at different cutoff values in a cohort of 333 patients with newly diagnosed myeloma and 92 patients with relapsed myeloma.
  
  
  RESULTS
  We found that nearly all IgH-related arrangements were observed in a large majority of the purified plasma cells; however, 13q deletion, 17p deletion, and 1q21 amplification appeared in different percentages within the malignant plasma cell population. Based on the size of subclones carrying these cytogenetic aberrations, the patients were divided into four groups: 0%-10%, 10.5%-20%, 20.5%-50%, and >50%. Receiver-operating characteristics analysis was applied to determine the optimal cutoff value with the greatest differential survival and showed that the most powerful clone sizes were 10% for 13q deletion, 50% for 17p deletion, and 20% for 1q21 gains, which provided the best possible cutoffs for predicting poor outcomes.
  
  
  CONCLUSIONS
  Our study indicated that the impact of clone size on prognostic value varies between specific genetic abnormalities. Prognostic value was observed for even a subgroup of plasma cells harboring the cytogenetic aberration of 13q deletion and 1q21 gains; however, 17p deletion displayed the most powerful cutoff for predicting survival only if the predominant clones harbored the abnormality.
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Gang
authors: G
authors: An
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Zengjun
authors: Z
authors: Li
authors: LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Yu-Tzu
authors: YT
authors: Tai
authors: LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Chirag
authors: C
authors: Acharya
authors: Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors: Qian
authors: Q
authors: Li
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Xiaoqi
authors: X
authors: Qin
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Shuhua
authors: S
authors: Yi
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Yan
authors: Y
authors: Xu
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China. LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Xiaoyan
authors: X
authors: Feng
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Chengwen
authors: C
authors: Li
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Jiawei
authors: J
authors: Zhao
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Lihui
authors: L
authors: Shi
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Meirong
authors: M
authors: Zang
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Shuhui
authors: S
authors: Deng
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Weiwei
authors: W
authors: Sui
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Mu
authors: M
authors: Hao
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Dehui
authors: D
authors: Zou
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Yaozhong
authors: Y
authors: Zhao
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Junyuan
authors: J
authors: Qi
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Tao
authors: T
authors: Cheng
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Kun
authors: K
authors: Ru
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors: Jianxiang
authors: J
authors: Wang
authors: LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. qiulg@ihcams.ac.cn kenneth_anderson@dfci.harvard.edu.
authors: Kenneth C
authors: KC
authors: Anderson
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China. qiulg@ihcams.ac.cn kenneth_anderson@dfci.harvard.edu.
authors: Lugui
authors: L
authors: Qiu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069286:Bortezomib / Q000008:administration & dosage; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000008:administration & dosage; D020732:Cytogenetic Analysis; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011379:Prognosis; D013792:Thalidomide / Q000008:administration & dosage
chemical_list: D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide