Abstract
Natural killer (NK) cells are lymphocytes with a large granular lymphocyte morphology, a CD3-CD56+ phenotype, a nonmajor histocompatibility complex-restricted cytotoxicity, and germline configuration T-cell receptor genes. NK cell lineage tumors originate from either precursor NK cells or mature NK cells.Tumors originating conceivably from precursor NK cells include myeloid/NK cell precursor acute leukemia, precursor NK cell acute lymphoblastic leukemia, and blastic NK cell lymphoma. However, because the developmental pathway of normal NK cells and the characteristics of these NK precursors are not fully understood, the definition and characterization of the tumors are only provisional.Tumors of mature NK cell origin include aggressive NK cell leukemia/lymphoma, nasal-type NK cell lymphoma, and chronic NK lymphocytosis, but the last disorder seems to be reactive in most cases. Because NK cell tumors are rare and difficult to manage, vigorous studies are required for their understanding and management.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Trinchieri G. Biology of natural killer cells.Adv Immunol. 1989;47: 187–376.
Hercend T, Schmidt RE. Characteristics and uses of natural killer cells.Immunol Today. 1988;9:291–293.
Robertson MJ, Ritz J. Biology and clinical relevance of human natural killer cells.Blood. 1990;76:2421–2438.
Oshimi K. Lymphoproliferative disorders of natural killer cells.Int J Hematol. 1996;63:279–290.
Lanier LL, Spits H, Phillips JH. The developmental relationship between NK cells and T cells.Immunol Today. 1992;13:392–395.
Sanchez MJ, Muench MO, Roncarolo MG, Roncarlo MG, Lanier LL, Phillips JH. Identification of a common T/natural killer cell progenitor in human fetal thymus.J Exp Med. 1994; 180:569–576.
Spits H, Lanier LL, Phillips JH. Development of human T and natural killer cells.Blood. 1995;85:2654–2670.
Spits H, Blom B, Jaleco A-C, et al. Early stages in the development of human T, natural killer and thymic dendritic cells.Immunol Rev. 1998;165:75–86.
Oshimi K. Provisional classification and diagnostic criteria of NKcell tumors proposed by the NK-Cell Tumor Study Group [in Japanese].Ketsueki-Schuyou-ka. 2000;40:87–88.
Suzuki R, Yamamoto K, Seto M, et al. CD7+ and CD56+ myeloid/ natural killer cell precursor acute leukemia: a distinct hematolymphoid disease entity.Blood. 1997;90:2417–2428.
Suzuki R, Nakamura S. Malignancies of natural killer (NK) cell precursor: myeloid/NK cell precursor acute leukemia and blastic NK cell lymphoma/leukemia.Leuk Res. 1999;23:615–624.
Suzuki R, Murata M, Kami M, et al. Prognostic significance of CD7+CD56+ phenotype and chromosome 5 abnormalities for acute myeloid leukemia M0.Int J Hematol. 2003;77:482–489.
Nakamura F, Tatsumi E, Kawano S, et al. Acute lymphoblastic leukemia/lymphoblastic lymphoma of natural killer (NK) lineage: quest for another NK-lineage neoplasm.Blood. 1997;89: 4665–4666.
Chaperot L, Bendriss N, Manches O, et al. Identification of a leukemic counterpart of the plasmacytoid dendritic cells.Blood. 2001;97: 3210–3217.
Feuillard J, Jacob M-C, Valensi F, et al. Clinical and biologic features of CD4+CD56+ malignancies.Blood. 2002;99:1556–1563.
Leroux D, Mugneret F, Callanan M, et al. CD4+, CD56+ DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe Francais de Cytogenetique Hematologique.Blood. 2002;99:4154–4159.
Petrella T, Comeau MR, Maynadie M, et al. “Agranular CD4+ CD56+ hematodermic neoplasm” (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes.Am J Surg Pathol. 2002;26:852–862.
Imamura N, Kusunoki Y, Kawa-Ha K, et al. Aggressive natural killer cell leukemia/lymphoma: report of four cases and review of the literature: possible existence of a new clinical entity originating from the third lineage of lymphoid cells.Br J Haematol. 1990;75: 49–59.
Mori KL, Egashira M, Oshimi K. Differentiation stage of natural killer cell-lineage lymphoproliferative disorders based on phenotypic analysis.Br J Haematol. 2001;115:225–228.
Oshimi K,Yamada O, Kaneko T, et al. Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders.Leukemia. 1993;7:782–788.
Yamamoto T, Iwasaki T,Watanabe N, et al. Expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells of patients with granular lymphocyte-proliferative disorders.Blood. 1993;81:1342–1346.
Yamaguchi M, Kita K, Miwa H, et al. Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells.Cancer. 1995;76:2351–2356.
Egashira M, Kawamata N, Sugimoto K, Kaneko T, Oshimi K. P-glycoprotein expression on normal and abnormally expanded natural killer cells and inhibition of P-glycoprotein function by cyclosporin A and its analogue, PSC833.Blood. 1999;93:599–606.
Trambas C,Wang Z, Cianfriglia M,Woods G. Evidence that natural killer cells express mini P-glycoproteins but not classic 170 kDa P-glycoprotein.Br J Haematol. 2001;114:177–184.
Wong KF, Zhang YM, Chan JKC. Cytogenetic abnormalities in natural killer cell lymphoma/leukaemia: is there a consistent pattern?Leuk Lymphoma. 1999;34:241–250.
Siu LLP,Wong K-F, Chan JKC, Kwong YL. Comparative genomic hybridization analysis of natural killer cell lymphoma/leukemia: recognition of consistent patterns of genetic alterations.Am J Pathol. 1999;155:1419–1425.
Siu LLP, Chan V, Chan JKC,Wong KF, Liang R, Kwong YL. Consistent patterns of allelic loss in natural killer cell lymphoma.Am J Pathol. 2000;157:1803–1809.
Wong KF. Genetic changes in natural killer cell neoplasms.Leuk Res. 2002;26:977–978.
Li T, Hongyo T, Syaifudin M, et al. Mutations in the p53 gene in nasal NK/T-cell lymphoma.Lab Invest. 2000;80:493–499.
Sakajiri S, Kawamata N, Egashira M, Mori K, Oshimi K. Molecular analysis of tumor suppressor genes,Rb, p53, p16INK4A, p15INK4B and p14ARF in natural killer cell neoplasms.Jpn J Cancer Res. 2001;92:1048–1056.
Sugimoto K, Kawamata N, Sakajiri S, Oshimi K. Molecular analysis of oncogenes,ras family genes (N-ras, K-ras, H-ras),myc family genes (c-myc, N-myc) andmdm2 in natural killer cell neoplasms.Jpn J Cancer Res. 2002;93:1270–1277.
Oshimi K. NK cell lymphoma.Int J Hematol. 2002;76(suppl 2): 118–121.
Emile J-F, Boulland M-L, Haioun C, et al. CD5-CD56+ T-cell receptor silent peripheral T-cell lymphomas are natural killer cell lymphomas.Blood. 1996;87:1466–1473.
Shikama N, Izuno I, Oguchi M, et al. Clinical stage IE primary lymphoma of the nasal cavity: radiation therapy and chemotherapy.Radiology. 1997;204:467–470.
Li Y-X, Coucke PA, Li J-Y, et al. Primary non-Hodgkin’s lymphoma of the nasal cavity: prognostic significance of paranasal extension and the roles of radiotherapy and chemotherapy.Cancer. 1998;83:449–456.
Kim GE, Cho JH, Yang WL, et al. Angiocentric lymphoma of the head and neck: patterns of systemic failure after radiation treatment.J Clin Oncol. 2000;18:54–63.
Yamaguchi M, Ogawa S, Nomoto Y, et al. Treatment outcome of nasal NK-cell lymphoma: a report of 12 consecutively-diagnosed cases and a review of the literature.J Clin Exp Hematopathol. 2001; 41:93–99.
Liang R,Todd D, Chan TK, et al. Treatment outcome and prognostic factors for primary nasal lymphoma.J Clin Oncol. 1995;13: 666–670.
Cheung MMC, Chan JKC, Lau WH, et al. Primary non-Hodgkin’s lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients.J Clin Oncol. 1998;16:70–77.
Kitoh T, Sawada M, Shirahase K, et al. Asparagine synthetase protein expression in leukemia cells: application of L-asparaginase treatment for leukemia [abstract].Blood. 1998;92(suppl 1):400a.
KitohT, SuzukiT, Nagafuji K, et al. Identification of L-asparaginasesensitive nasal natural killer/natural killer-likeT-cell lymphoma: usefulness of immunostaining result for asparagine synthetase in lymphoma cells [in Japanese].Ketsueki-Schuyou-ka. 2003;46:108–109.
Nagafuji K, Fujisaki T, Arima F, Ohshima K. L-asparaginase induced durable remission of relapsed nasal NK/T-cell lymphoma after autologous peripheral blood stem cell transplantation.Int J Hematol. 2001;74:447–450.
Liang R, Chen F, Lee CK, et al. Autologous bone marrow transplantation for primary nasal T/NK cell lymphoma.Bone Marrow Transplant. 1997;19:91–93.
Takenaka K, Shinagawa K, Maeda Y, et al. High-dose chemotherapy with hematopoietic stem cell transplantation is effective for nasal-type CD56+ natural killer cell lymphomas.Leuk Lymphoma. 2001;42:1297–1303.
Tefferi A, Li C-Y,Witzig TE, Dhodapkar MV, Okuno SH, Phyliky RL. Chronic natural killer cell lymphocytosis: a descriptive clinical study.Blood. 1994;84:2721–2725.
Nash R, McSweeney P, Zambello R, Semenzato G, Loughran TP Jr. Clonal studies of CD3- lymphoproliferative disease of granular lymphocytes.Blood. 1993;81:2363–2368.