CD94 transcripts imply a better prognosis in nasal-type extranodal NK/T-cell lymphoma

Lin, Chung-Wu; Chen, Yuhua; Chuang, Yi-Chun; Liu, Ting-Yun; Hsu, Su-Ming

doi:10.1182/blood-2003-01-0295

Cited by 35 publications

(24 citation statements)

References 41 publications

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“…For instance, P53 missense mutations have been associated with an aggressive course, 54 whereas overexpression of CD94, an NK-cell antigen receptor, has been shown to predict a favorable outcome. 55 In the present study, we show for the first time that high level of expression of the putative antiapoptotic protein PI9 by lymphoma cells is, unexpectedly, associated with a favorable outcome. This is in contrast with a previous report in anaplastic large-cell lymphoma 23 showing that PI9 expression by neoplastic cells was associated with a poor outcome, an observation in keeping with the hypothesis that tumor cells use expression of PI9 to escape their elimination mediated by the release of GrB by cytotoxic cells.…”

Section: Discussionmentioning

confidence: 82%

Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials

Bossard

Belhadj

Reyes

et al. 2006

Blood

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Nasal NK/T-cell lymphoma is a rare disease entity with a poor outcome. Expression of antiapoptotic proteins has not been extensively investigated in this entity. Forty-eight patients with nasal T/NKcell lymphoma who received first-line polychemotherapy (n ‫؍‬ 44) or chemoradiotherapy (n ‫؍‬ 4) were analyzed for expression of active caspase-3 (aC3), granzyme B protease inhibitor 9 (PI9), and Bcl-2 proteins. Lymphomas were CD3 ؉ / CD5 ؊ /granzyme B ؉ and EBV-associated. Median age was 46 years. Stage I/II disease was present in 75% of the cases and an International Prognostic Index (IPI) score less than 1 in 65%. With a median follow-up of 6.3 years, 5-year event-free survival (EFS) and overall survival (OS) rates were 39% and 49%, respectively. Apoptotic index was scored as high in 32% of cases and PI9 expression as positive in 68%, whereas 35% disclosed a high number of aC3 ؉ tumor cells. Univariate analysis showed that absence of PI9 and low apoptotic index were associated with poor outcome, but not aC3 expression nor IPI score. By multivariate analysis, both parameters affected independently EFS (P ‫؍‬ .02 and .08, respectively) and OS (P ‫؍‬ .009 and .04). In view of its constitutive expression by normal NK cells, it is suggested that loss of PI9 expression in tumor cells may reflect some mechanism associated with progression. (Blood. 2007;109:2183-2189)

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Section: Discussionmentioning

confidence: 82%

Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials

Bossard

Belhadj

Reyes

et al. 2006

Blood

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“…Increased expression of Fas-ligand is commonly seen in ENKL, but this is nonspecific and seen in a number of aggressive lymphomas 55,[60][61][62] . NK inhibitory receptors, such as CD94 or NKG2A are also expressed in NK-cell neoplasms, but such expression is not uniform or consistent [63][64][65][66][67] . However, expression of CD94 is reported to confer a better prognosis in ENKL 67 .…”

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confidence: 99%

“…NK inhibitory receptors, such as CD94 or NKG2A are also expressed in NK-cell neoplasms, but such expression is not uniform or consistent [63][64][65][66][67] . However, expression of CD94 is reported to confer a better prognosis in ENKL 67 . EBV is found in the tumor cells in virtually all cases, and ENKL, nasal-type is now regarded as an EBV-related neoplasm [68][69][70] .…”

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confidence: 99%

Leukemia and Lymphoma of Natural Killer Cells

Suzuki

2005

J Clin Exp Hematopathol

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Malignant hematolymphoid disorders arising from NK cells have become widely recognized over the past decade. The two forms of NK-cell malignancy, aggressive NK-cell leukemia (ANKL) and extranodal NK-cell lymphoma of nasal type (ENKL) are both characterized by the proliferation of tumor cells with an NK-cell like immunophenotype. ANKL usually presents with bone marrow tumor cells accompanied by circulating leukemic cells, and hepatosplenomegalay is a common clinical feature. ENKL most frequently affects the nasal or paranasal regions, with cutaneous involvement also being common. Approximately 70 percent of ENKL present with localized tumor cells, and follow an indolent clinical course, but, in advanced cases, tumors rapidly expand and are frequently fatal. Tumor cells from both ANKL and ENKL are surface CD3 − and CD56 + but differ in their expression of CD16. Epstein-Barr virus (EBV) is found in most cases of NK-cell leukemia/lymphoma, suggesting an oncogenic role, but patients may have biclonal or polyclonal populations of malignant cells based on differential EBV genome incorporation. NK-cell neoplasms are frequently resistant to chemotherapy due to p-glycoprotein expression and associated multidrug resistance. The prognoses of both localized and advanced stages of NK-cell malignancies are worse than most other lymphoid malignancies, but studies are currently underway to assess the safety and efficacy of novel chemoradiotherapy regimens for the treatment of these neoplasms.

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“…[3][4][5][6] Even with intensive therapies combining multiagent chemotherapy and involved-field radiotherapy, the prognosis of NKTCL remains poor, with 5-year overall survival ranging from 42% to 64% in 4 recent studies, [7][8][9][10] and novel alternative approaches are needed. Several factors have been incriminated to account for aggressiveness or poor outcome, including Fas and p53 mutations, 11,12 expression of the multidrug resistance 1 (MDR1) gene product P-glycoprotein, 13 absence of CD94 transcript, 14 and gzm B inhibitor PI9. 9 However, the mechanisms involved in resistance to therapy remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type

Huang

Reyniès

Leval

et al. 2010

Blood

291

287

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Biopsies and cell lines of natural killer/ T-cell lymphoma, nasal type (NKTCL)were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared with peripheral T-cell lymphoma, not otherwise specified, NKTCL had greater transcript levels for NK-cell and cytotoxic molecules, especially granzyme H. Compared with normal NKcells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, Epstein-Barr Virus-induced genes, and PDGFRA. Notably, platelet-derived growth factor receptor ␣ and its phosphorylated form were confirmed at the protein level, and in vitro the MEC04 NKTCL cell line was sensitive to imatinib. Deregulation of the AKT, Janus kinase-signal transducers and activators of transcription, and nuclear factor-B pathways was corroborated by nuclear expression of phosphorylated AKT, signal transducers and activators of transcription 3, and RelA in NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 [1q44]

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CD94 transcripts imply a better prognosis in nasal-type extranodal NK/T-cell lymphoma

Cited by 35 publications

References 41 publications

Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials

Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials

Leukemia and Lymphoma of Natural Killer Cells

Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type

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