scholarly journals A novel lncRNA TCLlnc1 promotes peripheral T cell lymphoma progression through acting as a modular scaffold of HNRNPD and YBX1 complexes

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Ping Zhao ◽  
Meng-Meng Ji ◽  
Ying Fang ◽  
Xiao Li ◽  
Hong-Mei Yi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Small Interfering Rnas ◽  
Transcription Activator ◽  
Peripheral T Cell Lymphoma

AbstractLong noncoding RNAs (lncRNAs) play an essential role in tumor progression. Few researches focused on the clinical and biological relevance of lncRNAs in peripheral T cell lymphoma (PTCL). In this research, a novel lncRNA (ENST00000503502) was identified overexpressed in the main subtypes of PTCL, and designated as T cell lymphoma-associated lncRNA1 (TCLlnc1). Serum TCLlnc1 was associated with extranodal involvement, high-risk International Prognostic Index, and poor prognosis of the patients. Both in vitro and in vivo, overexpression of TCLlnc1 promoted T-lymphoma cell proliferation and migration, both of which were counteracted by the knockdown of TCLlnc1 using small interfering RNAs. As the mechanism of action, TCLlnc1 directly interacted with transcription activator heterogeneous nuclear ribonucleoprotein D (HNRNPD) and Y-box binding protein-1 (YBX1) by acting as a modular scaffold. TCLlnc1/HNRNPD/YBX1 complex upregulated transcription of TGFB2 and TGFBR1 genes, activated the tumor growth factor-β signaling pathway, resulting in lymphoma progression, and might be a potential target in PTCL.

scholarly journals Baseline and interim functional imaging with PET effectively risk stratifies patients with peripheral T-cell lymphoma

2019 ◽  
Vol 3 (2) ◽  
pp. 187-197 ◽  
Author(s):  
Neha Mehta-Shah ◽  
Kimiteru Ito ◽  
Kurt Bantilan ◽  
Alison J. Moskowitz ◽  
Craig Sauter ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
T Cell ◽  
Confidence Interval ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Standardized Uptake Value ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma

Abstract The prognosis of peripheral T-cell lymphoma (PTCL) is heterogenous. Baseline or interim imaging characteristics may inform risk-adapted treatment paradigms. We identified 112 patients with PTCL who were consecutively treated with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)/CHOP-like regimens with the intent to consolidate with an autologous transplant. Baseline (n = 93) and interim (after 4 cycles, n = 99) positron emission tomography (PET) images were reevaluated, and we calculated baseline total metabolic tumor volume (TMTV). Interim PET (iPET) responses were graded visually by 5-point score (i5PS) and by percentage change of standardized uptake value. By univariate analysis, predictors of event-free survival (EFS) included Prognostic Index for Peripheral TCL (PIT) higher than 1 (hazard ratio [HR], 1.83; P = .021), International Prognostic Index (IPI) higher than 3 (HR, 2.01; P = .021), high TMTV (>125 cm3; HR, 3.92; P = .003), and positive iPET (HR, 3.57; P < .001). By multivariate analysis, high baseline TMTV predicted worse overall survival (OS; HR, 6.025; P = .022) and EFS (HR, 3.861; P = .005). Patients with i5PS of 1 to 3 had a longer median OS and EFS (104 months, 64 months) than those with i5PS of 4 to 5 (19 months, 11 months; P < .001). Four-year OS and EFS for patients with i5PS of 1 to 3 and PIT of 1 or less were 85% and 62%, respectively. However, 4-year OS and EFS for those with i5PS of 4 to 5 and PIT higher than 1 were both 0% (P < .001). In multivariate analysis, after controlling for IPI and PIT, i5PS was independently prognostic for EFS (HR, 3.400 95% confidence interval, 1.750-6.750; P < .001) and OS (HR, 10.243; 95% confidence interval, 4.052-25.891; P < .001). In conjunction with clinical parameters, iPET helps risk stratify patients with PTCL and could inform risk-adapted treatment strategies. Prospective studies are needed to confirm these findings.

scholarly journals Enteropathy-associated T-cell lymphoma: clinical and histological findings from the International Peripheral T-Cell Lymphoma Project

Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 148-155 ◽  
Author(s):  
Jan Delabie ◽  
Harald Holte ◽  
Julie M. Vose ◽  
Fred Ullrich ◽  
Elaine S. Jaffe ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
World Health ◽  
Peripheral T Cell Lymphoma

Abstract Few large, international series of enteropathy-associated T-cell lymphoma (EATL) have been reported. We studied a cohort of 62 patients with EATL among 1153 patients with peripheral T-cell or natural killer (NK)–cell lymphoma from 22 centers worldwide. The diagnosis was made by a consensus panel of 4 expert hematopathologists using World Health Organization (WHO) criteria. Clinical correlations and survival analyses were performed. EATL comprised 5.4% of all lymphomas in the study and was most common in Europe (9.1%), followed by North America (5.8%) and Asia (1.9%). EATL type 1 was more common (66%) than type 2 (34%), and was especially frequent in Europe (79%). A clinical diagnosis of celiac sprue was made in 32.2% of the patients and was associated with both EATL type 1 and type 2. The median overall survival was only 10 months, and the median failure-free survival was only 6 months. The International Prognostic Index (IPI) was not as good a predictor of survival as the Prognostic Index for Peripheral T-Cell Lymphoma (PIT). Clinical sprue predicted for adverse survival independently of the PIT. Neither EATL subtype nor other biologic parameters accurately predicted survival. Our study confirms the poor prognosis of patients with EATL and the need for improved treatment options.

Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project

Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 3931-3937 ◽  
Author(s):  
Wing-yan Au ◽  
Dennis D. Weisenburger ◽  
Tanin Intragumtornchai ◽  
Shigeo Nakamura ◽  
Won-Seog Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Clinical Features ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Clinical Feature ◽  
Peripheral T Cell Lymphoma ◽  
Nk T Cell

Abstract Among 1153 new adult cases of peripheral/T-cell lymphoma from 1990-2002 at 22 centers in 13 countries, 136 cases (11.8%) of extranodal natural killer (NK)/T-cell lymphoma were identified (nasal 68%, extranasal 26%, aggressive/unclassifiable 6%). The disease frequency was higher in Asian than in Western countries and in Continental Asia than in Japan. There were no differences in age, sex, ethnicity, or immunophenotypic profile between the nasal and extranasal cases, but the latter had more adverse clinical features. The median overall survival (OS) was better in nasal compared with the extranasal cases in early- (2.96 vs 0.36 years, P < .001) and late-stage disease (0.8 vs 0.28 years, P = .031). The addition of radiotherapy for early-stage nasal cases yielded survival benefit (P = .045). Among nasal cases, both the International Prognostic Index (P = .006) and Korean NK/T-cell Prognostic Index (P < .001) were prognostic. In addition, Ki67 proliferation greater than 50%, transformed tumor cells greater than 40%, elevated C-reactive protein level (CRP), anemia (< 11 g/dL) and thrombocytopenia (< 150 × 109/L) predicts poorer OS for nasal disease. No histologic or clinical feature was predictive in extranasal disease. We conclude that the clinical features and treatment response of extranasal NK/T-cell lymphoma are different from of those of nasal lymphoma. However, the underlying features responsible for these differences remain to be defined.

scholarly journals Pretreatment Whole Blood Epstein-Barr Viremia Is a Prognostic Factor in Peripheral T-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4143-4143
Author(s):  
Yu Ri Kim ◽  
Soo-Jeong Kim ◽  
June-Won Cheong ◽  
Hyewon Lee ◽  
Haerim Chung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
T Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival

Abstract Abstract Peripheral T-cell lymphoma (PTCL) is the highly aggressive lymphoid malignancies, treatment outcome is very poor. There are increasing evidence about the role of Epstein-Barr virus (EBV) in PTCL. Because of its rarity, there was few studies about the prognostic factors incorporating EBV in PTCL. The aim of this study was to evaluate the role of EBV as prognostic factors in PTCL. We retrospectively reviewed the 174 PTCL patients (peripheral T-cell lymphoma, not otherwise specified; n=123, anaplastic large cell lymphoma; n=19, angioimmunoblastic T-cell lymphoma; n=26, enteropathy related T-cell lymphoma, n=5, hepatosplenic gammadelta T-cell lymphoma; n=1). Median age of the patients was 63 (20~94) years with 107 (61.5%) male patients. One-year OS and PFS was 55.5%, 37.5%, respectively. Stage 3 or 4 patients were 150 (86.2%). Bone marrow involvement were detected 73 (42.0%) patients among 163 available patients. For IPI scores, 29 (16.7%) patients were classified as low risk, 42 (24.1%) as low-intermediate risk, 57 (32.8%) as high-intermediate risk, and 46 (26.4%) as high risk. For PIT scores, 18 (11.1%) patients were classified in group 1, 41 (25.2%) in group 2, 58 (35.6%) in group 3, and 46 (28.2%) in group 4. Upfront autologous hematopoietic stem cell transplantation (n=17) improved OS and PFS (P=0.001 and P<0.001, respectively). In univariate analysis, poor performance status (ECOG ¡Ã2) (P <0.001 and P <0.001, respectively), low absolute lymphocyte counts (<1000/mm3) (P=0.022 and P=0.038, respectively), high ferritin (¡Ã1,000/mm3) (P =0.002 and P =0.002, respectively), EBV viremia in the whole blood (positive) (P=0.016 and P <0.001, respectively), low protein level (<6.3 g/dL) (P <0.001 and P <0.001, respectively) and low albumin level (<3.5 g/dL) (P =0.001 and P =0.001, respectively) were related with inferior OS and PFS. High international prognostic index (IPI) and prognostic index for PTCLu (PIT) were related with inferior OS and PFS (P<0.001, P=0.029 and P=0.019, P=0.278, respectively) (Figure 1A, 1B, 2A, 2B). In multivariate analysis, poor performance status, extranodal involvement more than one site and EBV viremia were related with OS and PFS in multivariate analysis. (P <0.001, P =0.024, P =0.001 and P =0.001, P=0.002, P=0.031, respectively). We made a new prognostic score model using statistically significant 3 variables in multivariate analysis: low, no adverse factors; intermediate, one factor; high, two or three factors. This model could identify three groups of patients for OS and PFS (Figure 3A,3B.) This study suggests that prognostic models including EBV for PTCL showed good risk classification. There will be need to investigate the mechanism of EBV and specific treatment strategy for EBV-related patients. These patients will be need to consider more effective therapeutic strategy to improve the poor survival in PTCL. Figure 1. Overall survival and progression free survival according to international prognostic index Figure 1. Overall survival and progression free survival according to international prognostic index Figure 2. Overall survival and progression free survival according to prognostic index for PTCLu Figure 2. Overall survival and progression free survival according to prognostic index for PTCLu Figure 3. Overall survival and progression free survival according to new prognostic model Figure 3. Overall survival and progression free survival according to new prognostic model Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinicopathologic Characteristics of Angioimmunoblastic T-Cell Lymphoma: Analysis of the International Peripheral T-Cell Lymphoma Project

2013 ◽  
Vol 31 (2) ◽  
pp. 240-246 ◽  
Author(s):  
Massimo Federico ◽  
Thomas Rudiger ◽  
Monica Bellei ◽  
Bharat N. Nathwani ◽  
Stefano Luminari ◽  
...  
Keyword(s):  
T Cell ◽  
Survival Data ◽  
Cell Lymphoma ◽  
Risk Group ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Angioimmunoblastic T Cell Lymphoma

PurposeThe International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-cell and natural killer (NK) –cell lymphomas.Patients and MethodsAngioimmunoblastic T-cell lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated.ResultsOf 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age ≥ 60 years, stages III to IV disease, lactic dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance status (PS) ≥ 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age ≥ 60 years, PS ≥ 2, LDH > normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years, PS ≥ 2, ENSs > one, B symptoms, and platelet count < 150 × 109/L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P = .0065).ConclusionAITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies.

Peripheral T-Cell Lymphoma, Not Otherwise Specified: A Clinicopathologic Study of 340 Cases from the International T-Cell Lymphoma Project.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2458-2458
Author(s):  
Dennis D. Weisenburger ◽  
Wyndham H. Wilson ◽  
Julie M. Vose
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Transformed Cells ◽  
Entire Group ◽  
Peripheral T Cell Lymphoma ◽  
Not Otherwise Specified ◽  
Pathologic Features

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is an uncommon lymphoma in which the clinical and pathological features of prognostic importance are not well understood. Therefore, we collected 340 cases of PTCL-NOS from 21 centers in 13 countries around the world to study this entity. PTCL-NOS was the most common subtype of PTCL in the project (29.3%) and consisted mainly of PTCL unspecified (88.5%) and the lymphoepithelial type (8.2%). The median age of the patients was 60 years, 66% were males, and 69% had stage III/IV disease at diagnosis. Anthracycline-based chemotherapy was given in 80% and a complete response was obtained in 56% of the patients. However, the 5-year overall and failure-free survivals for the entire group were only 32% and 20%, respectively. The International Prognostic Index (IPI) was highly predictive of survival (p<0.001). Other clinical prognostic factors identified in multivariate analysis (MVA) included hypergammaglobulinemia (HR 0.5), mass >10 cm (HR 2.5), and platelets <150,000/mm3 (HR 2.2). Pathologic features predictive of survival included >70% transformed cells (HR 1.7) and <10% CD8+ background T-cells (HR 1.8). However, in final MVA, only the IPI and >70% transformed cells were predictive of survival. In conclusion, PTCL-NOS is an aggressive disease in which the IPI and the percentage of transformed cells could be used to select patients for risk-adapted therapies.

scholarly journals Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Koen Debackere ◽  
Lukas Marcelis ◽  
Sofie Demeyer ◽  
Marlies Vanden Bempt ◽  
Nicole Mentens ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Lymphoma ◽  
Ex Vivo ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Fusion Transcripts ◽  
Not Otherwise Specified

AbstractPeripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases. We identify FYN-TRAF3IP2, KHDRBS1-LCK and SIN3A-FOXO1 as new in-frame fusion transcripts, with FYN-TRAF3IP2 as a recurrent fusion detected in 8 of 55 cases. Using ex vivo and in vivo experiments, we demonstrate that FYN-TRAF3IP2 and KHDRBS1-LCK activate signaling pathways downstream of the T cell receptor (TCR) complex and confer therapeutic vulnerability to clinically available drugs.

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