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Long non‐coding RNA MALAT 1 is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma
Author(s) -
Handa Hiroshi,
Kuroda Yuko,
Kimura Kei,
Masuda Yuta,
Hattori Hikaru,
Alkebsi Lobna,
Matsumoto Morio,
Kasamatsu Tetsuhiro,
Kobayashi Nobuhiko,
Tahara Kenichi,
Takizawa Makiko,
Koiso Hiromi,
Ishizaki Takuma,
Shimizu Hiroaki,
Yokohama Akihiko,
Tsukamoto Norifumi,
Saito Takayuki,
Murakami Hirokazu
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14882
Subject(s) - multiple myeloma , cancer research , bortezomib , downregulation and upregulation , chemotherapy , pathogenesis , gene expression , biology , bone marrow , gene , medicine , immunology , genetics
Summary Extramedullary myeloma ( EMM ) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo‐resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT 1 is a highly abundantly and ubiquitously expressed long non‐coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT 1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure. MALAT 1 expression was significantly higher in multiple myeloma ( MM ) than in monoclonal gammopathy of undetermined significance. Furthermore, MALAT 1 expression was markedly higher in EMM compared with that in corresponding intramedullary myeloma cells. A higher MALAT 1 level was associated with shorter overall and progression‐free survival. MALAT 1 expression level was positively correlated with expression of HSP 90 AA 1, HSP 90 AB 1 and HSP 90B1 but not with TP 53 expression. MALAT 1 was significantly upregulated by bortezomib and doxorubicin. Considering the known functions of MALAT 1 , our results suggest that it acts as a stress response gene that is upregulated by chemotherapy, thereby linking chemotherapy to EMM formation. Elucidating the biological implication of long non‐coding RNA contributes to deeper understanding concerning the pathogenesis and investigation of novel therapeutic targets for MM .