Frequent CD7 Antigen Loss in Aggressive Natural Killer-Cell Leukemia: A Useful Diagnostic Marker
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Background : Aggressive natural killer-cell leukemia (ANKL) is a rare neoplasm characterized by systemic proliferation of NK cells. However, the differential diagnosis of NK lymphoproliferative disorders is difficult because of the absence of a distinct diagnostic hallmark. Therefore, to identify diagnostic markers for ANKL, we analyzed the clinical data and laboratory findings obtained for 20 patients with ANKL. Methods : From January 2000 to July 2007, 20 patients were diagnosed with ANKL on the basis of bone marrow studies. We retrospectively analyzed the clinical features and laboratory findings, including the complete blood count, Epstein-Barr virus status, immunophenotype, and the cytogenetic results. Results : The subjects included 6 women and 14 men (median age, 44 yr; range, 2-70 yr). Cytogenetic studies were performed in 18 patients, and karyotypic abnormalities were observed in 9 patients (50%). None of the cytogenetic abnormalities were constantly observed in all the patients. However, 6q abnormalities were observed in 4 patients (4/18, 22%). The immunophenotype of the leukemic NKcells was cytoplasmic CD3+, surface CD3-, CD16/56+, CD2+, and CD5-. Notably, the CD7 antigen was absent in 10 patients (50%). When the CD7 loss was combined with cytogenetic abnormalities, clonal markers could be identified in 75% of the ANKL cases. Conclusions : The CD7 antigen loss was frequently observed in our series of ANKL patients. In conjunction with the cytogenetic findings, this characteristic immunophenotypic finding can serve as a reliable marker for the timely diagnosis of ANKL. Therefore, immunophenotypic analysis of CD7 expression should be included in the diagnosis of NK cell neoplasms.
Abstract
Background : Aggressive natural killer-cell leukemia (ANKL) is a rare neoplasm characterized by systemic proliferation of NK cells. However, the differential diagnosis of NK lymphoproliferative disorders is difficult because of the absence of a distinct diagnostic hallmark. Therefore, to identify diagnostic markers for ANKL, we analyzed the clinical data and laboratory findings obtained for 20 patients with ANKL. Methods : From January 2000 to July 2007, 20 patients were diagnosed with ANKL on the basis of bone marrow studies. We retrospectively analyzed the clinical features and laboratory findings, including the complete blood count, Epstein-Barr virus status, immunophenotype, and the cytogenetic results. Results : The subjects included 6 women and 14 men (median age, 44 yr; range, 2-70 yr). Cytogenetic studies were performed in 18 patients, and karyotypic abnormalities were observed in 9 patients (50%). None of the cytogenetic abnormalities were constantly observed in all the patients. However, 6q abnormalities were observed in 4 patients (4/18, 22%). The immunophenotype of the leukemic NKcells was cytoplasmic CD3+, surface CD3-, CD16/56+, CD2+, and CD5-. Notably, the CD7 antigen was absent in 10 patients (50%). When the CD7 loss was combined with cytogenetic abnormalities, clonal markers could be identified in 75% of the ANKL cases. Conclusions : The CD7 antigen loss was frequently observed in our series of ANKL patients. In conjunction with the cytogenetic findings, this characteristic immunophenotypic finding can serve as a reliable marker for the timely diagnosis of ANKL. Therefore, immunophenotypic analysis of CD7 expression should be included in the diagnosis of NK cell neoplasms.
참고문헌 (25)
- Jaffe ES HN, "World health classification of tumo-urs: Pathology and genetics of tumors of haematopoietic and lymphoid tissues. in: Aggressive NK-cell leukaemia", pp.198~200 (2001), IARC Press
- Loughran TP Jr, "Clonal diseases of large granular lymphocytes", Blood, 82, pp.1~14 (1993)
- Ruskova A, "Aggressive natural killer-cell leukemia:report of five cases and review of the literature", Leuk Lymphoma, 45, pp.2427~2438 (2004)
- Hart DN, "Epstein-Barr viral DNA in acute large granular lymphocyte (natural killer) leukemic cells", Blood, 79, pp.2116~2123 (1992)
- Song SY, "Aggressive natural killer cell leukemia: clinical features and treatment outcome", Haematologica, 87, pp.1343~1345 (2002)
- Kanavaros P, "Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus", Blood, 81, pp.2688~2695 (1993)
- Chan JK, "Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm", Blood, 89, pp.4501~4513 (1997)
- Ko YH, "REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features. Hematolymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American lymphoma", Cancer, 83, pp.806~812 (1998)
- Sokol L, "Large granular lymphocyte leukemia", Oncologist, 11, pp.263~273 (2006)
- Suzuki R, "Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells", Leukemia, 18, pp.763~770 (2004)
- Spits H, "Early stages in the development of human T, natural killer and thymic dendritic cells", Immunol Rev, 165, pp.75~86 (1998)
- Drexler HG, "Malignant hematopoietic cell lines: in vitro models for the study of natural killer cell leukemia-lymphoma", Leukemia, 14, pp.777~782 (2000)
- Spits H, "Development of human T and natural killer cells", Blood, 85, pp.2654~2670 (1995)
- Miller JS, "Differentiation of natural killer (NK) cells from human primitive marrow progenitors in a stroma-based long-term culture system: identification of a CD34+7+ NK progenitors", Blood, 83, pp.2594~2601 (1994)
- Ware RE, "T cell CD7 mRNA expression is regulated by both transcriptional and post-transcriptional mechanisms", Int Immunol, 5, pp.179~187 (1993)
- Pace KE, "CD7 delivers a pro-apoptotic signal during galectin-1-induced T cell death", J Immunol, 165, pp.2331~2334 (2000)
- Sempowski GD, "Structure and function of the CD7 molecule", Crit Rev Immunol, 19, pp.331~348 (1999)
- Jamal S, "Immunophenotypic analysis of peripheral T-cell neoplasms. A multiparameter flow cytometric approach", Am J Clin Pathol, 116, pp.512~526 (2001)
- Oshimi K, "Progress in understanding and managing natural killercell malignancies", Br J Haematol, 139, pp.532~544 (2007)
- Kawa-Ha K, "CD3-negative lymphoproliferative disease of granular lymphocytes containing Epstein-Barr viral DNA", J Clin Invest, 84, pp.51~55 (1989)
- Harabuchi Y, "Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma", Lancet, 335, pp.128~130 (1990)
- Rowlands DC, "Epstein-Barr virus and carcinomas: rare association of the virus with gastric adenocarcinomas", Br J Cancer, 68, pp.1014~1019 (1993)
- Delecluse HJ, "Epstein-Barr virusassociated tumours: an update for the attention of the working pathologist", J Clin Pathol, 60, pp.1358~1364 (2007)
- Wong KF, "Cytogenetic abnormalities in natural killer cell lymphoma", leukaemia--is there a consistent pattern?, 1999, pp.34, 241~250
- Weidmann E, "Hepatosplenic T cell lymphoma. A review on 45 cases since the first report describing the disease as a distinct lymphoma entity in 1990", Leukemia, 14, pp.991~997 (2000)