scholarly journals Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type

2010 ◽  
Vol 21 (5) ◽  
pp. 1032-1040 ◽  
Author(s):  
R. Suzuki ◽  
J. Suzumiya ◽  
M. Yamaguchi ◽  
S. Nakamura ◽  
J. Kameoka ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Cell Leukemia ◽  
Nasal Type

scholarly journals Nonnasal Lymphoma Expressing the Natural Killer Cell Marker CD56: A Clinicopathologic Study of 49 Cases of an Uncommon Aggressive Neoplasm

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4501-4513 ◽  
Author(s):  
John K.C. Chan ◽  
V.C. Sin ◽  
K.F. Wong ◽  
C.S. Ng ◽  
William Y.W. Tsang ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Leukemia ◽  
Neoplastic Cells ◽  
Prolymphocytic Leukemia ◽  
Nasal Type ◽  
Nk T Cell

Abstract Expression of the natural killer (NK) cell antigen CD56 is uncommon among lymphomas, and those that do are almost exclusively of non–B-cell lineage and show a predilection for the nasal and nasopharyngeal region. This study analyzes 49 cases of nonnasal CD56+ lymphomas, the largest series to date, to characterize the clinicopathologic spectrum of these rare neoplasms. All patients were Chinese. Four categories could be delineated. (1) Nasal-type NK/T cell lymphoma (n = 34) patients were adults 21 to 76 years of age (median, 50 years), including 25 men and 9 women. They presented with extranodal disease, usually in multiple sites. The commonest sites of involvement were skin, upper aerodigestive tract, testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%) apparently had stage I disease. The neoplastic cells were often pleomorphic, with irregular nuclei and granular chromatin, and angiocentric growth was common. The characteristic immunophenotype was CD2+ CD3/Leu4− CD3ε+ CD56+, and 32 cases (94%) harbored Epstein-Barr virus (EBV). Follow-up information was available in 29 cases: 24 died at a median of 3.5 months; 3 were alive with relapse at 5 months to 2.5 years; and 2 were alive and well at 3 and 5 years, respectively. (2) Aggressive NK cell leukemia/lymphoma (n = 5) patients presented with hepatomegaly and blood/marrow involvement, sometimes accompanied by splenomegaly or lymphadenopathy. The neoplastic cells often had round nuclei and azurophilic granules in the pale cytoplasm. All cases exhibited an immunophenotype of CD2+ CD3/Leu4− CD56+ CD16− CD57− and all were EBV+. All of these patients died within 6 weeks. (3) In blastoid NK cell lymphoma (n = 2), the lymphoma cells resembled those of lymphoblastic or myeloid leukemia. One case studied for CD2 was negative and both cases were EBV−. One patient was alive with disease at 10 months and one was a recent case. (4) Other specific lymphoma types with CD56 expression (n = 8) included one case each of hepatosplenic γδ T-cell lymphoma and S100 protein+ T-cell lymphoproliferative disease and two cases each of T-chronic lymphocytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histiocytic lymphoma. All of these cases were EBV−. Six patients died at a median of 6.5 months. Nonnasal CD56+ lymphomas are heterogeneous, but all pursue a highly aggressive clinical course. The nasal-type NK/T-cell lymphoma and aggressive NK cell leukemia/lymphoma show distinctive clinicopathologic features and a very strong association with EBV. Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.

Prognostic value of hemoglobin in natural killer cell lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17557-17557
Author(s):  
J. Xiao ◽  
T. Lin ◽  
Y. Cao ◽  
X. Fu ◽  
C. Guo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Natural Killer ◽  
Prognostic Value ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Southern China ◽  
Univariate Analysis ◽  
Stage I

17557 Background: Natural Killer (NK) cell lymphoma is a group of increasingly recognized but poorly defined disease entities. This study investigated its clinical features and prognostic factors for southern China population. Methods: Patients with pathologically confirmed NK cell lymphoma in one center since 1999 to 2004 were included. Central histological and immunohistochemical review was undertaken to every case. The major study endpoint was overall survival. Survival curves were estimated by the Kaplan-Meier method. Detailed clinical, pathological and laboratory data were included in univariate analysis and statistically significant factors in univariate analysis were then included in multivariate analysis. Results: Totally 64 eligible patients were identified. Of these, 59 patients were extranodal NK cell lymphoma nasal type, 3 patients were aggressive NK cell lymphoma and 2 patients were blastic NK cell lymphoma. From the basic analysis, 47% of the patients had stage I disease, 42% were stage II, 11% were stage III or IV. B-symptoms were present in 39%. 73% of these patients had International Prognostic Index (IPI) 0 or 1. Before treatment, 25% complicated with anemia. As to the therapy, 38% received chemotherapy alone, 3% received radiotherapy alone and 59% received a multidisciplinary therapy. After initial therapy, 59% achieved CR, 22% achieved PR and 19% were refractory disease. With a median follow-up duration of 20 months, the median overall survival was 28 months (95% CI: 10, 45). Hb lower than 110 g/l before treatment was statistically significant in multivariate analysis (p = 0.031). Presenting B-symptoms and ECOG PS score higher than 1 were also independent prognostic factors (P = 0.001 and 0.006 respectively). Conclusions: The outcome of patients with NK cell lymphoma was poor even for Stage I or II cases. Our data suggested Hemoglobin < 110 g/l had more prognostic value than IPI and Ann Arbor staging system for NK cell lymphoma in southern China, but it needs further confirmation. No significant financial relationships to disclose.

scholarly journals Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Harinder Gill ◽  
Raymond H. S. Liang ◽  
Eric Tse
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Hematopoietic Stem ◽  
Nasal Type

The World Health Organization (WHO) classification recognizes 2 main categories of natural killer (NK) cell-derived neoplasms, namely, extranodal NK/T-cell lymphoma, nasal type, and aggressive NK-cell leukaemia. Extranodal nasal NK/T-cell lymphoma is more frequent in the Far East and Latin America. Histopathological and immunophenotypical hallmarks include angiocentricity, angiodestruction, expression of cytoplasmic CD3 epsilon (ε), CD56, and cytotoxic molecules and evidence of Epstein-Barr virus (EBV) infection. Early stage disease, in particular for localized lesion in the nasal region, is treated with chemotherapy and involved-field radiotherapy. On the other hand, multiagent chemotherapy is the mainstay of treatment for advanced or disseminated disease. L-asparaginase-containing regimens have shown promise in treating this condition. The role of autologous hematopoietic stem cell transplantation is yet to be clearly defined. Allogeneic hematopoietic stem cell transplantation, with the putative graft-versus-lymphoma effect, offers a potentially curative option in patients with advanced disease.

Dysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma

Blood ◽  
2011 ◽  
Vol 118 (18) ◽  
pp. 4919-4929 ◽  
Author(s):  
Siok-Bian Ng ◽  
Junli Yan ◽  
Gaofeng Huang ◽  
Viknesvaran Selvarajan ◽  
Jim Liang-Seah Tay ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Mirna Expression ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Nasal Type ◽  
Natural Killer T Cell ◽  
Killer T Cell

Abstract We performed a comprehensive genome-wide miRNA expression profiling of extranodal nasal-type natural killer/T-cell lymphoma (NKTL) using formalin-fixed paraffin-embedded tissue (n = 30) and NK cell lines (n = 6) compared with normal NK cells, with the objective of understanding the pathogenetic role of miRNA deregulation in NKTL. Compared with normal NK cells, differentially expressed miRNAs in NKTL are predominantly down-regulated. Re-expression of down-regulated miRNAs, such as miR-101, miR-26a, miR26b, miR-28-5, and miR-363, reduced the growth of the NK cell line and modulated the expression of their predicted target genes, suggesting the potential functional role of the deregulated miRNAs in the oncogenesis of NKTL. Taken together, the predicted targets whose expression is inversely correlated with the expression of deregulated miRNA in NKTL are significantly enriched for genes involved in cell cycle-related, p53, and MAPK signaling pathways. We also performed immunohistochemical validation for selected target proteins and found overexpression of MUM1, BLIMP1, and STMN1 in NKTL, and notably, a corresponding increase in MYC expression. Because MYC is known to cause repression of miRNA expression, it is possible that MYC activation in NKTL may contribute to the suppression of the miRNAs regulating MUM1, BLIMP1, and STMN1.

Involvement of STAT3 Transcription Factor in Disseminated Nasal-Type Natural Killer Cell Lymphomas.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4167-4167
Author(s):  
Paul Coppo ◽  
Valérie Gouilleux-Gruart ◽  
Sandrine Bouchet ◽  
Yenlin Huang ◽  
Peggy Dartigues ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Natural Killer ◽  
Target Genes ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Killer Cell ◽  
Dominant Negative ◽  
Malignant Cells ◽  
Nasal Type ◽  
Stat3 Phosphorylation

Abstract Disseminated nasal-type natural killer (NK) cell lymphoma is an aggressive disease with very poor prognosis. The usual chemoresistance of this disease led us to explore the possible role of the transcription factor STAT3 in oncogenesis. For this, we established and characterized a continuous interleukin (IL)2-dependent NK cell line (MEC04) from a patient with a fatal nasal-type NK cell lymphoma. MEC04 cells phenotype was CD3−, CD7+, TCR−, CD16−, CD56+bright, p58−, p70−, NKP−, and NKG2A+, they harbored poor cytotoxic activity against K562 cells, and spontaneously secreted interferon-γ, IL-10 and vascular-endothelium growth factor in vitro, suggesting that malignant cells arise from the CD56+bright regulatory NK cell population. Injection of MEC04 cells to NOD/SCID mice led to a fatal multiorgan infiltration by malignant cells. We show by immunohistochemistry that STAT3 is phosphorylated in Y705 dimerization residue in MEC04 and YT cell lines, and on biopsies from 6/6 patients with nasal-type NK cell lymphoma, suggesting that STAT3 may be oncogenic in this disease. By contrast, Y705 residue was not phosphorylated on 2 patients with hepatosplenic γδT-cell lymphoma. By confocal microscopy, we showed that STAT3 was located in nucleus in MEC04 cells. Y705 STAT3 phosphorylation involved JAK2, since exposure of cells to AG490 inhibitor inhibited Y705 STAT3 phosphorylation, and correlated in a dose-dependent growth inhibition at 24 hours and 48 hours. By using transducible TAT-STAT3b or TAT-STAT3Y705F recombinant proteins (a dominant-negative form of STAT3 [STAT3b isoform], and a STAT3 protein mutated on Y705 residue which prevents STAT3 dimerization [STAT3Y705F]), we were able to demonstrate that inhibition of STAT3 activation increased mortality and decreased proliferation by more than 50 p. cent at 24 hours and 48 hours, which correlated with decreased expression of 2 STAT3 target genes (Bcl-XL and c-Myc). These results suggest that STAT3 protein has a major role in the oncogenic process of nasal-type NK cell lymphomas, and may thus represent a promising therapeutical target.

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