Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

Iqbal, Javeed; Weisenburger, D. D.; Chowdhury, Aparajita; Tsai, Ming Ying; Srivastava, Gopesh; Greiner, Timothy C.; Küçük, Can; Deffenbacher, Karen; Vose, Julie M.; Smith, Lynette M.; Au, Wing Y.; Nakamura, Shigeo; Seto, Masao; Delabie, Jan; Berger, Françoise; Loong, Florence; Ko, Young‐Hyeh; Sng, Ivy; Liu, X.; Loughran, Thomas P.; Armitage, Jamés O.; Chan, Wing C.

doi:10.1038/leu.2010.255

Cited by 137 publications

(164 citation statements)

References 49 publications

(61 reference statements)

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“…In addition, specific and exclusive expression of a single KIR family gene member, KIR2DL4, was observed, which suggests a possible oncogenic role for it during the transformation of NK cells. This observation is consistent but more extreme than previous reports showing dominant expression of KIR2DL4 in NKTCL cases using other methodologies such as DNA microarray, 4 RT-PCR, 24 or flow cytometry. 25 This difference using different methodologies for quantification of expression may be due to the following reasons: KIR mRNA sequences are highly similar, and DNA microarray probe sets are not as specific as RNA-seq for the measurement of the expression of individual KIR genes.…”

Section: Discussionsupporting

confidence: 91%

“…KIR family gene expression data for NKTCL cases and NK-cell lines were obtained from our earlier study, 4 which used the GeneChip Human Genome U133 Plus version 2.0 DNA microarray platform (Affymetrix, Inc.). The raw files of the microarray data are available from Gene Expression Omnibus (http://www.…”

Section: Gene Expression Profilingmentioning

confidence: 99%

“…2 NKTCL cases show good response to radiotherapy in stage I disease; however, the prognosis is markedly worse in patients with more advanced stages of the disease. 3 Most NKTCLs originate from transformed NK-cells, 4 and due to lack of NK-cell receptors with unique rearrangements, diagnostic markers of clonality have been challenging to identify.…”

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confidence: 99%

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Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma

Küçük

Gong

et al. 2016

The American Journal of Pathology

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Natural killer/T-cell lymphoma (NKTCL) is a rare, aggressive form of non-Hodgkin lymphoma that is generally incurable at more advanced stages with systemic involvement. Clonal diagnostic markers (eg, unique T-or B-cell receptor rearrangements) are not available for NKTCLs. Killer cell immunoglobulin like receptors (KIRs) are a family of type I transmembrane glycoproteins involved in the inhibition or activation of NK cells. A restricted expression profile of KIRs has been proposed as clonal markers of NK-cell proliferations. Here we evaluated the transcription profile of all KIR family genes and C-type lectin receptor genes using RNA sequencing on NKTCL cases (n Z 17) and NK-cell lines (n Z 3). The expression of all KIRs tended to be markedly reduced or absent in NKTCL, except for the KIR family member killer Ig-like receptor 2DL4 (KIR2DL4; alias CD158D), which was selectively overexpressed in the majority (59%) of cases. No specific expression pattern was observed for C-type lectin receptors. KIR2DL4 is an unusual member of the KIR family that recognizes human leukocyte antigen G and mediates NK-cell activation through inducing proliferation and survival pathways such as AKT and NF-kB. Stable knockdown of KIR2DL4 in two malignant NK-cell lines with high KIR2DL4 expression significantly reduced cell growth. Selective overexpression of KIR2DL4 and downregulation of inhibitory KIRs may contribute to NKTCL pathogenesis. (Am J Pathol 2016, 186: 1435e1441; http://dx

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Section: Discussionsupporting

confidence: 91%

Section: Gene Expression Profilingmentioning

confidence: 99%

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Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma

Küçük

Gong

et al. 2016

The American Journal of Pathology

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“…A group of gd T-cell lymphomas share profiling features with NK-cell lymphomas. 59 Burkitt's lymphoma and B-cell lymphoma unclassifiable with features intermediate between BL and DLBCL. Two studies have described the GEP of BL that refine the differential diagnosis with DLBCL.…”

Section: Characterization Of Known Entities and Recognition Of New Camentioning

confidence: 99%

Whole genome profiling and other high throughput technologies in lymphoid neoplasms—current contributions and future hopes

Campo

2013

Modern Pathology

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The development of high throughput technologies based on the knowledge of the human genome has opened the possibility to search for global genomic alterations in tumors responsible for their development and progression that may have important clinical implications. One of the major applications of this genomic knowledge has been the design of different types of microarray platforms for the analysis of DNA alterations and gene expression profiling (GEP). The main contributions of the DNA studies in lymphoid neoplasms include the definition of relatively characteristic genomic profiles for specific disease entities, the demonstration of common chromosomal alterations across entities, the identification of genes and pathways targeted by the altered chromosomal regions, and the identification of chromosomal alterations with prognostic implications. RNA GEP studies in these tumors have enhanced the molecular characterization of known entities and facilitated the recognition of new subtypes and categories of lymphoid neoplasms, the identification of new biomarkers and prognostic models, and the detection of oncogenic pathways with potential implications for targeted therapies. The recent development of the next generation sequencing (NGS) technologies and its application in lymphoid neoplasms already have provided an initial view of the complex landscape of somatic mutations in these tumors and some findings with important functional and clinical implications. This review addresses the major contributions and limitations of the microarray technologies in the understanding of lymphoid neoplasms and discusses how this knowledge may be transferred into the clinics. The initial results of the NGS studies are also presented.

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“…Studies have also demonstrated genetic aberrations related to important functions, including apoptosis (FAS), cell cycle (TP73, CDKN2A, CDKN2B, and CDKN1A), signaling pathways (KIT, CTNNB1, and JAK3), tumor-suppressor genes (TP53, PRDM1, AIM1, FOXO3, and HACE1), and oncogenes (RAS/KRAS/HRAS and MYC) [89]. Although the molecular profile of ENKL, nasal type, differs from that of other PTCLs, a subset of extranodal lymphomas derived from cd T cells has a molecular signature that is very similar to that of ENKL, nasal type [90] (Fig. 5).…”

Section: Epstein-barr Virus (Ebv)-associated T-or Nk-cell Lymphoprolimentioning

confidence: 99%

Peripheral T cell lymphoma in Asia

Park

2014

Int J Hematol

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Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-and NK-cell neoplasms, the incidence of which is higher in Asian countries than in Western countries. Although its etiology is mainly unknown, several risk factors (such as genetic factors, abnormal immunity, environmental factors, and infectious causes) have been proposed. PTCL are classified based on a combination of several parameters, including morphology, site of presentation, viral status, immunophenotype, and specific genetic alterations. Their classification is ongoing, with the emergence of new entities and refinement of existing entities because of the development of diagnostic markers and new genetic alterations. This review presents epidemiologic data for PTCL in Asia, together with recent progress in the pathology of PTCL compared with the WHO 2008 classification.Epidemiology T-and NK-cell lymphomas are uncommon: overall, they represent fewer than 25 % of all non-Hodgkin's lymphoma (NHL) [1][2][3]. The occurrence rates of various subtypes of T-and NK-cell lymphomas in Asia are significantly different from those observed in Western countries, and even among Asian countries. The incidence and distribution of T-and NK-cell lymphomas in several Asian countries is summarized in Fig. 1 and Table 1 [ [4][5][6][7][8][9][10][11][12][13][14][15].The frequencies of T-and NK-cell lymphomas seem to increase from West to East Asia. The occurrence rate of Tand NK-cell lymphomas are relatively low (\20 % of NHL) mainly in West Asia (Turkey 16.2 %, Iraq 19 %, and Kuwait 18 %) and South Asia (Pakistan 11.3 %, and India 20.2 %), but relatively high mainly in East Asia (China 32.5 %, Korea 22 %, and Japan 24.9 %) and Southeast Asia (Thailand 25 %). The proportion of T-and NK-cell lymphomas in Taiwan is very low (13.3 %) compared with that of other East Asian countries. Regarding the subtypes of T-and NK-cell lymphomas, two West (Turkey and Iraq) and one South (Pakistan) Asian countries share similar distribution patterns, presenting T lymphoblastic lymphoma (T-LBL) as the most common subtype, followed by peripheral T-cell lymphoma (PTCL) or anaplastic largecell lymphoma (ALCL). The frequency of mycosis fungoides/sezary syndrome (MF/SS) is very high in Kuwait. The distribution patterns of T-and NK-cell lymphomas in Thailand, Taiwan, and Korea are similar, whereas adult T-cell leukemia/lymphoma (ATLL) represents a high proportion of T-and NK-cell lymphomas in Japan. When ATLL is excluded, four countries (Thailand, Taiwan, Korea, and Japan) exhibit very similar patterns of subtype distribution of T-and NK-cell lymphomas. Extranodal NK/ T-cell lymphoma (ENKL) is frequent in China (48 %) and Korea (28.7 %), but is less frequent in Japan (10.4 %), as reported by a recent study performed by an international T-cell project [2]. In China, the frequency of T-or NK-cell lymphoma varies according to geographic region

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Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

Cited by 137 publications

References 49 publications

Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma

Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma

Whole genome profiling and other high throughput technologies in lymphoid neoplasms—current contributions and future hopes

Peripheral T cell lymphoma in Asia

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