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LR11: a novel biomarker identified in follicular lymphoma
Author(s) -
Kawaguchi Takeharu,
Ohwada Chikako,
Takeuchi Masahiro,
Shimizu Naomi,
Sakaida Emiko,
Takeda Yusuke,
Sakai Shio,
Tsukamoto Shokichi,
Yamazaki Atsuko,
Sugita Yasumasa,
Jiang Meizi,
Higashi Morihiro,
Yokote Koutaro,
Tamaru Junichi,
Bujo Hideaki,
Nakaseko Chiaki
Publication year - 2013
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.12467
Subject(s) - follicular lymphoma , biomarker , medicine , lymphoma , oncology , follicular phase , cancer research , pathology , biology , genetics
Follicular lymphoma (FL) is the second most frequent type of non-Hodgkin lymphoma and is incurable by combination chemotherapies (Salles & Ghesquieres, 2012). Although the Follicular Lymphoma International Prognostic Index-2 (FLIPI-2) is predictive for progression-free survival (PFS) (Federico et al, 2009), widely adapted biomarkers that are directly released from FL tumour cells have not been established to date. LR11 (also called SORL1 or SorLA) is a type I membrane protein that plays a key role in the migration of undifferentiated vascular smooth muscle cells (Jiang et al, 2008), and circulating soluble LR11 (sLR11) is a biomarker for coronary stenosis (Takahashi et al, 2010). The potent action of sLR11 is mediated by the urokinase-type plasminogen activator receptor (uPAR)/integrin-mediated activation of focal adhesion kinase (FAK)/ERK/Rac1 cascades (Ohwaki et al, 2007). LR11 is also expressed in human CD34CD38 immature haematopoietic precursors (Zhang et al, 2000), but little is known about its potential role in haematopoietic cells. We have recently found that LR11 is highly expressed in leukaemic cells and that serum sLR11 levels in acute leukaemia patients are significantly increased at diagnosis and normalize at remission (Sakai et al, 2012). Here we analysed the expression profile of LR11 in FL cells and evaluated the clinical importance of serum sLR11 levels in FL patients. Tumour specimens and serum samples were collected from 61 newly diagnosed, untreated FL patients attending Chiba University Hospital and affiliated hospitals between 2002 and 2012. Fifty-two patients (85.2%) were treated with the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) regimen, 3 (4.9%) with irradiation only, and 6 (9.8%) were observed without treatment (see Table SI for patients’ characteristics). Paired serum samples at diagnosis and remission were obtained in 20 patients. Normal controls were serum samples collected from 75 healthy adult volunteers who had given informed consent.