Kwong YL. Natural killer-cell malignancies: diagnosis and treatment

Department of Medicine, University of Hong Kong, Hong Kong, China.
Leukemia (Impact Factor: 10.43). 01/2006; 19(12):2186-94. DOI: 10.1038/sj.leu.2403955
Source: PubMed


Natural killer (NK)-cell malignancies are uncommon diseases. Previously known as polymorphic reticulosis or angiocentric T-cell lymphomas, they are classified by the World Health Organization as NK/T-cell lymphoma, nasal type and aggressive NK-cell leukemia. They are prevalent in Asia and South America, but exceptionally rare in western countries. Pathologically, NK-cell lymphomas show a polymorphic neoplastic infiltrate with an angioinvasive and angiodestructive pattern. Lymphoma cells are characteristically CD2+, CD56+ and cytoplasmic CD3epsilon+. T-cell receptor gene is germline, and clonal Epstein-Barr virus (EBV) infection is almost invariably. Clinically, they can be divided into nasal, non-nasal, and aggressive lymphoma/leukemia subtypes. Most nasal NK-cell lymphomas present with stage I/II disease, and frontline radiotherapy is the most important key to successful treatment. Many stage I/II patients treated with radiotherapy fail systemically, implying that concomitant chemotherapy may be needed. Chemotherapy is indicated for advanced nasal NK-cell lymphoma, and the non-nasal and aggressive subtypes. However, treatment results are unsatisfactory. High-dose chemotherapy with hematopoietic stem cell transplantation may be beneficial to selected patients. The International Prognostic Index and presentation EBV DNA load is of prognostic significance and may be useful in the stratification of patients for various treatment modalities.

4 Reads
  • Source
    • "These novel effects of statins may be of clinical importance given that natural killer cell leukemias tend to be very difficult to treat with standard chemotherapy regimens. The only approach that has been shown to be successful with some aggressive natural killer cell leukemias has been allogeneic bone marrow transplantation [3,21]. Given that life spans following the diagnosis of an aggressive natural killer cell leukemia is generally measured in months [2], patients need more effective approaches for this type of leukemia. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Natural killer cells comprise the body's first line of defense against virus-infected cells. As is true of all lymphocytes, natural killer cell malignancies can develop, however natural killer cell leukemias can be very difficult to treat due to their intrinsic resistance to chemotherapeutic agents. With the recent understanding that statin drugs may have anti-cancer properties, our investigations have focused on the ability of statins to inhibit the growth and cytotoxicity of the YT-INDY natural killer cell leukemia cell line. Our findings indicate that several statin compounds can inhibit YT-INDY proliferation disrupt cell cycle progression and abrogate natural killer cell cytotoxicity. Since natural killer cell leukemia cytotoxicity may play a role in the pulmonary damage seen in these patients, this is an important finding. Cytotoxicity, proliferation and cell cycle progression could be restored by the addition of mevalonate, signifying that the statin effects are brought about through HMG CoA reductase inhibition. The mevalonate pathway intermediate geranylgeranyl pyrophosphate, but not other intermediates in the mevalonate pathway, partially reversed statin-induced inhibition of YT-INDY proliferation and cytotoxicity. These results suggest that blockage of products made in the latter part of the mevalonate pathway may account for the observed inhibitory effects on YT-INDY proliferation and cytotoxicity. However, geranylgeranyl pyrophosphate could not reverse the statin-induced inhibition of the cell cycle. These results suggest that the statin drugs should be investigated as a potential therapeutic strategy for human natural killer cell leukemias possibly in combination with chemotherapeutic agents.
    12/2013; 1(1):33. DOI:10.1186/2050-7771-1-33
  • Source
    • "Others include extranodal NK/T lymphoma, nasal type (ENKL), and aggressive NK cell leukemia (ANKL). Although such EBV-positive T/NK LPDs are relatively rare, therapeutic treatment for those disorders is challenging, and the prognosis of those patients often can be dismal [4], [5]. Therefore, development of effective and specific drugs is an important goal. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epstein-Barr virus (EBV) LMP1 is a major oncoprotein expressed in latent infection. It functions as a TNFR family member and constitutively activates cellular signals, such as NFκB, MAPK, JAK/STAT and AKT. We here screened small molecule inhibitors and isolated HSP90 inhibitors, Radicicol and 17-AAG, as candidates that suppress LMP1 expression and cell proliferation not only in EBV-positive SNK6 Natural Killer (NK) cell lymphoma cells, but also in B and T cells. Tumor formation in immuno-defficient NOD/Shi-scid/IL-2Rγ(null) (NOG) mice was also retarded. These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.
    PLoS ONE 05/2013; 8(5):e63566. DOI:10.1371/journal.pone.0063566 · 3.23 Impact Factor
  • Source
    • "Occasionally, NKcell lymphomas can arise in extranasal sites, involving the skin, gastrointestinal tract, salivary glands, and testis, and are referred to as non-nasal NK-cell lymphomas. Rarely, NK-cell lymphomas can present in a leukemic phase, and are referred to as NK-cell leukemia (Kwong, 2005). NK-cell neoplasms are rare but aggressive lymphomas uniformly associated with EBV infection. "
    [Show abstract] [Hide abstract]
    ABSTRACT: DNA methylation is an epigenetic alteration leading to heritable phenotypic changes of cells with functional consequences. It is important in early embryonic development, stem cell differentiation, and tissue-specific gene expression. In normal cells, promoter-associated CpG islands (CGI) are generally unmethylated except in X-chromosome inactivation or genomic imprinting. In cancer, tumor cells are characterized by global hypomethylation but locus-specific hypermethylation of promoter-associated CGI, resulting in gene silencing. MicroRNAs (miRNAs) are short, non-coding RNA sequences of 18-25 nucleotides, which can repress the translational of multiple protein-coding mRNAs by sequence-specific binding to the 3'untranslated region. Depending on the genes targeted, miRNA can be tumor suppressive if an oncogene is repressed, or it can be oncogenic when a tumor suppressive gene is repressed. Recently, aberrant methylation of tumor suppressive miRNAs has been reported in different types of cancers including lymphomas. Herein, we review the recent literature of methylation of tumor suppressive miRNAs in different histopathologic subtypes of lymphomas, and discuss its potential diagnostic, prognostic, and therapeutic significance.
    Frontiers in Genetics 11/2012; 3:233. DOI:10.3389/fgene.2012.00233
Show more

Preview (2 Sources)

4 Reads
Available from