Decreased MYC-associated factor X (MAX) expression is a new potential biomarker for adverse prognosis in anaplastic large cell lymphoma.
Yamashita Takahisa,Higashi Morihiro,Momose Shuji,Adachi Akiko,Watanabe Toshiki,Tanaka Yuka,Tokuhira Michihide,Kizaki Masahiro,Tamaru Jun-Ichi
Scientific reports
MYC-associated factor X (MAX) is a protein in the basic helix-loop-helix leucine zipper family, which is ubiquitously and constitutively expressed in various normal tissues and tumors. MAX protein mediates various cellular functions such as proliferation, differentiation, and apoptosis through the MYC-MAX protein complex. Recently, it has been reported that MYC regulates the proliferation of anaplastic large cell lymphoma. However, the expression and function of MAX in anaplastic large cell lymphoma remain to be elucidated. We herein investigated MAX expression in anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and found 11 of 37 patients (30%) with ALCL lacked MAX expression, whereas 15 of 15 patients (100%) with PTCL-NOS expressed MAX protein. ALCL patients lacking MAX expression had a significantly inferior prognosis compared with patients having MAX expression. Moreover, patients without MAX expression significantly had histological non-common variants, which were mainly detected in aggressive ALCL cases. Immunohistochemical analysis showed that MAX expression was related to the expression of MYC and cytotoxic molecules. These findings demonstrate that lack of MAX expression is a potential poor prognostic biomarker in ALCL and a candidate marker for differential diagnosis of ALCL and PTCL-NOS.
10.1038/s41598-020-67500-w
Validation of the RHL30 digital gene expression assay as a prognostic biomarker for relapsed Hodgkin lymphoma.
Calvente Lourdes,Tremblay-LeMay Rosemarie,Xu Wei,Chan Fong Chun,Hong Michael,Zhang Tong,Yhim Ho-Young,Kuruvilla John,Crump Michael,Kukreti Vishal,Prica Anca,Regier Dean,Marra Marco A,Karsan Aly,Steidl Christian,Scott David W,Sabatini Peter,Kridel Robert
British journal of haematology
Despite continuing improvements in the management of classical Hodgkin lymphoma (cHL), relapse remains associated with a risk of lymphoma-related mortality. The biological composition of relapse tumour biopsies shows interpatient variability, which can be leveraged to design prognostic biomarkers. Here, we validated the RHL30 assay, a previously reported gene expression model in an independent cohort of 41 patients with relapsed cHL. Patients classified as high-risk by the RHL30 assay had inferior failure-free survival (FFS) after autologous stem cell transplantation (2-year FFS 41% vs. 92%, P = 0·035). The RHL30 model is a robust biomarker that risk-stratifies patients considered for autologous stem cell transplantation.
10.1111/bjh.16777
Evaluation of serum thymidine kinase 1 activity as a biomarker for treatment effectiveness and prediction of relapse in dogs with non-Hodgkin lymphoma.
Boyé Pierre,Floch Franck,Serres François,Geeraert Kévyn,Clerson Pierre,Siomboing Xavier,Bergqvist Mattias,Sack Gabriel,Tierny Dominique
Journal of veterinary internal medicine
BACKGROUND:Serum thymidine kinase 1 (sTK1) activity is closely correlated with DNA synthesis. OBJECTIVES:Evaluate sTK1 activity as a biomarker for treatment response and early detection of relapse in dogs with lymphoma. ANIMALS:Ninety-seven client-owned dogs with naive or relapsed lymphoma and 23 healthy dogs. METHODS:Prospective study. Serum TK1 activity measured by refined ELISA-based method (DiviTum assay, Biovica International) before treatment, at clinical response, and every 4 weeks until relapse or last follow-up. RESULTS:Serum TK1 activity was ≤20 Du/L in 96% (22/23) of healthy dogs. Pretreatment sTK1 activity was >20 Du/L in 88% (85/97) dogs with lymphoma. At clinical response, sTK1 activity was significantly lower in dogs with complete (CR, n = 36) versus partial (PR, n = 29) response (P < .0001). Sensitivity (Se) and specificity (Sp) of sTK1 activity for detecting nonfully responders were 76% and 100%, respectively, with cutoff of 119.5 Du/L (AUC, 0.90; 95%-CI, 0.81-0.98; P < .0001). In dogs with CR, a 5-fold increase in sTK1 activity at a 4-week interval predicted relapse at the subsequent 4-week assessment with a Se 50% and Sp 94% (AUC, 0.72; 95%-CI, 0.55-0.90; P = .02). An increase of sTK1 activity (>2.7-fold value measured at clinical response) predicted relapse at subsequent 4-week assessment with a Se 61% and Sp 88% (AUC, 0.79; 95%-CI, 0.64-0.95; P = .004). CONCLUSIONS AND CLINICAL IMPORTANCE:Monitoring sTK1 activity could help to detect complete responders and early disease progression in dogs with lymphoma.
10.1111/jvim.15513
Novel biomarker, phosphorylated T-LAK cell-originated protein kinase (p-TOPK) can predict outcome in primary central nervous system lymphoma.
Koh Masaki,Hayakawa Yumiko,Akai Takuya,Hayashi Tomohide,Tomita Takahiro,Nagai Shoichi,Kuroda Satoshi
Neuropathology : official journal of the Japanese Society of Neuropathology
This study aimed to assess whether T-lymphokine-activated killer cell-originated protein kinase (TOPK) can be a potent novel biomarker to predict the outcome in patients with primary central nervous system lymphoma (PCNSL). This study enrolled 20 patients who were histologically diagnosed as having diffuse large B-cell type PCNSL between 2005 and 2015. Using surgical specimens, the expression of TOPK and phosphorylated TOPK (p-TOPK) was analyzed on immunohistochemistry. Clinical features such as age, sex, Karnofsky performance status (KPS), ocular involvement, deep brain structure involvement, the number of lesions, chemotherapy and radiation therapy were also collected. Impacts of TOPK/p-TOPK expression on their progression-free survival (PFS) and overall survival (OS) were examined with multivariate analysis. Median PFS/OS were 24.2 and 39.0 months, respectively. On immunostaining, the mean percentage of TOPK-positive cells was 35.5 ± 20.8%, and the mean number of p-TOPK-positive cells was 13.7 ± 15.7 cells/mm . The higher expression of p-TOPK was significantly related to multiple lesions (P = 0.003). Multivariate analysis demonstrated that only the higher expression of p-TOPK was an independent predictor to shorten both PFS (P = 0.029; hazard ratio (HR), 5.5; 95% confidential interval (CI), 1.2-25.3) and OS (P = 0.014; HR, 7.7; 95% CI, 1.5-41.3). These findings strongly suggest that p-TOPK may be a potent biomarker to determine the outcome of patients with PCNSL and to develop novel drugs to treat PCNSL.
10.1111/neup.12463
Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium.
Stevens Wendy B C,Mendeville Matias,Redd Robert,Clear Andrew J,Bladergroen Reno,Calaminici Maria,Rosenwald Andreas,Hoster Eva,Hiddemann Wolfgang,Gaulard Philippe,Xerri Luc,Salles Gilles,Klapper Wolfram,Pfreundschuh Michael,Jack Andrew,Gascoyne Randy D,Natkunam Yasodha,Advani Ranjana,Kimby Eva,Sander Birgitta,Sehn Laurie H,Hagenbeek Anton,Raemaekers John,Gribben John,Kersten Marie José,Ylstra Bauke,Weller Edie,de Jong Daphne
Haematologica
In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end of spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries. The criteria were: early failure, progression or lymphoma-related death <2 years long remission, response duration of >5 years. Immunohistochemical staining for T cells and macrophages was performed on tissue microarrays from initial biopsies and scored with a validated computer-assisted protocol. Shallow whole-genome and deep targeted sequencing was performed on the same samples. The 96/122 cases with complete molecular and immunohistochemical data were included in the analysis. wild-type (=0.006), gain of chromosome 18 (=0.002), low percentages of CD8+ cells (=0.011) and CD163+ areas (=0.038) were associated with early failure. No significant differences in other markers were observed, thereby refuting previous claims of their prognostic significance. Using an optimized study design, this Lunenburg Lymphoma Biomarker Consortium study substantiates wild-type status, gain of chromosome 18, low percentages of CD8+ cells and CD163+ area as predictors of early failure to immunochemotherapy in follicular lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP [-like]), while refuting the prognostic impact of various other markers.
10.3324/haematol.2017.165415