Prognostic relevance of protein expression, clinical factors, and MYD88 mutation in primary bone lymphoma

// Yong Xu 1, * , Jian Li 2, * , Jian Ouyang 1 , Juan Li 1 , Jingyan Xu 1 , Qiguo Zhang 1 , Yonggong Yang 1 , Min Zhou 1 , Jing Wang 1 , Cuiling Zhang 1 , Yueyi Xu 1 , Ping Li 1 , Rongfu Zhou 1 and Bing Chen 1 1 Department of Hematology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China 2 Department of Hematology Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, China * Authors contributed equally to this work Correspondence to: Rongfu Zhou, email: rfzhoucn@163.com Bing Chen, email: chenbing2004@126.com Keywords: primary bone lymphoma, JAK/STAT, MYD88 Received: May 25, 2017      Accepted: July 25, 2017      Published: August 04, 2017 ABSTRACT Primary bone lymphomas (PBLs) are composed of malignant lymphoid cells presenting in osseous sites, without supra-regional lymph node or extranodal involvement. We systematically characterized the immunophenotype and the myeloid differentiation factor 88 ( MYD88 )-L265P gene mutation status in PBL. Clinical data from 19 patients with PBL treated at Nanjing Drum Tower Hospital between 2009 and 2015 were analyzed retrospectively. Protein expression patterns were identified immunohistochemically, and MYD88 mutation was assessed using polymerase chain reaction and direct DNA sequencing. Fifteen patients presented with diffuse large B-cell lymphoma. Clinical factors favoring a good prognosis were an age < 60 years and rituximab treatment. B-cell lymphoma 2 expression was detected in 5/15 diffuse large B-cell lymphoma patients, and was associated with a poor prognosis in a univariate model. Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling factors were upregulated in PBLs. All eighteen evaluable PBL samples harbored wild-type MYD88. These data thus suggest that age and rituximab treatment are independent prognostic factors determining overall survival, and that activation of JAK/STAT3 signaling may promote the pathogenesis of PBL. Moreover, the absence of MYD88 -L265P mutation in PBL indicate there are distinct pathogenetic backgrounds among extranodal lymphomas.