Heterogeneous chromosome 12p deletion is an independent adverse prognostic factor and resistant to bortezomib-based therapy in multiple myeloma
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Fei Li1,2, Yan Xu1, Ping Deng4, Ye Yang5, Weiwei Sui1, Fengyan Jin6, Mu Hao1, Zengjun Li1, Meirong Zang1, Dehui Zhou1, Zhimin Gu5, Kun Ru1, Jianxiang Wang1, Tao Cheng1, Lugui Qiu1,3
1State 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
2Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
3Umbilical Cord Blood Bank of Tianjin, Tianjin 300020, China
4Department of Science and Education, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
5Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA
6Tumor Center, The First Hospital of Jilin University, Changchun 130021, China
Lugui Qiu, e-mail: [email protected]
Keywords: 12p13 deletion, CD27 gene, prognosis, bortezomib, multiple myeloma
Received: January 09, 2015 Accepted: February 08, 2015 Published: March 20, 2015
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.
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