Expression of Cyclin-Dependent Kinase 6 (cdk6) and Frequent Loss of CD44 in Nasal-Nasopharyngeal NK/T-Cell Lymphomas: Comparison with CD56-Negative Peripheral T-Cell Lymphomas

Lien, Han‐Chung; Lin, Chun-Wu; Huang, Pei‐Hsin; Chang, Min-Lee; Hsu, Su-Ming

doi:10.1038/labinvest.3780093

Cited by 31 publications

(26 citation statements)

References 49 publications

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“…4) ϩ . This is consistent with our previous report that frequent loss of CD44 and strong expression of CDK6 distinguishes SNLs from PTLs (Lien et al, 2000). The CD44 and CDK6 status of r-KIR ϩ /r-TCR ϩ SNLs was more like r-KIR ϩ /r-TCR Ϫ SNLs rather than PTLs.…”

Section: Correlation With Immunohistochemistrysupporting

confidence: 82%

Presence of Restricted Killer Immunoglobulin-Like Receptor Repertoire and Monoclonal T-Cell Receptor γ Rearrangement as Evidence of Mixed NK/T-Cell Differentiation in a Subset of Sinonasal Lymphomas

Lin

Yang

Chuang

et al. 2003

Laboratory Investigation

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SUMMARY:Most sinonasal lymphomas have a restricted killer immunoglobulin-like receptor (KIR) repertoire without a monoclonal T-cell receptor-␥ (TCR-␥) rearrangement, implying an NK lineage. However, the lineage assignment of sinonasal lymphoma with a monoclonal TCR-␥ rearrangement is unclear because of its mixed NK/T phenotype. The possibility of a mixed NK/T lineage arises with the discovery of T cells with NK features, such as KIR ϩ T cells or V␣24 ϩ NKT cells. The former might transform into a T-cell lymphoma with both a monoclonal TCR-␥ rearrangement and a restricted KIR repertoire; the latter might give rise to a T-cell lymphoma with a monoclonal V␣24 rearrangement and possibly a restricted KIR repertoire. To identify such mixed-lineage lymphomas, we undertook a survey of 15 consecutive sinonasal lymphomas and found six with both a restricted KIR repertoire and a monoclonal TCR-␥ rearrangement, consistent with KIR ϩ T-cell lymphomas. Among these six cases, four female CD56Ϫ cases constituted a distinct group with a better prognosis than the rest of the male cases of sinonasal lymphomas. None of the six cases had a monoclonal V␣24 repertoire, thus excluding a derivation from NKT cells. The predominance of KIR ϩ T cells that normally function in chronic viral infections over V␣24 ϩ NKT cells that typically recognize glycolipid antigens is consistent with the known association of Epstein-Barr virus infection with sinonasal lymphoma. The demonstration of mixed lineage in a mature lymphoid neoplasm is unusual and echoes the World Health Organization classification that placed NK-cell and T-cell lymphomas in a mixed group. (Lab Invest 2003, 83:55-64).

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Section: Correlation With Immunohistochemistrysupporting

confidence: 82%

Presence of Restricted Killer Immunoglobulin-Like Receptor Repertoire and Monoclonal T-Cell Receptor γ Rearrangement as Evidence of Mixed NK/T-Cell Differentiation in a Subset of Sinonasal Lymphomas

Lin

Yang

Chuang

et al. 2003

Laboratory Investigation

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“…However, recent studies shed light on the other D-type cyclin and its partner kinase. The cyclin D3 gene has been found to be the causative gene of non-Hodgkin B lymphoma, which was highly activated by chromosomal rearrangement in this neoplasm (Sonoki et al, 2001), and there are reports for the close association of overexpression of Cdk6 and D3 with certain human cancers (Costello et al, 1997;Timmermann et al, 1997;Easton et al, 1998;Corcoran et al, 1999;Lien et al, 2000;Ebert et al, 2001;Shaughnessy et al, 2001). Moreover, our recent findings suggest that Cdk6, associated with cyclin D3 in particular, plays critical roles controlling a cell's proliferative competence and anchorage-independent proliferation (Jinno et al, 1999b;Lin et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, much less attention has been paid to Cdk6 and D3 until recently when several reports were made suggesting the possible involvement of Cdk6 and D3 in malignant transformation. The activity or amount of Cdk6 is elevated in some cancer cells and lymphomas (Costello et al, 1997;Timmermann et al, 1997;Corcoran et al, 1999;Lien et al, 2000). In non-Hodgkin B lymphoma, the cyclin D3 gene is highly activated by the chromosomal translocation, t(6; 14) (p21.1; q32.3), suggesting that cyclin D3 may be the causative oncogene (Sonoki et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Cdk6–cyclin D3 highly sensitizes cells to physical and chemical transformation

et al. 2003

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Virtually all mammalian cells express two seemingly redundant cyclin-D-dependent kinases (Cdk4 and Cdk6) and three partner cyclins (D1, D2 and D3) essential for the G 1 -S transition, with predominant expression of Cdk4 and D1 in mesenchymal cells and Cdk6 and D3 in hematopoietic cells. We recently found two novel functions for Cdk6 executed in fibroblasts although unlike Cdk4 it is dispensable for their proliferation. In the rat fibroblast NRK-49F cells, oncogenic stimulation recruits Cdk6 to participate in a step of the cell cycle start that seems to be critical for anchorage-independent S-phase onset. Among the kinase-D-type cyclin combinations, the Cdk6-cyclin-D3 complex has a unique ability to evade inhibition by cyclin-dependent kinase inhibitors and thereby control the cell's proliferative competence under growth-suppressive conditions. We describe here that 2-5-fold overexpression of both Cdk6 and D3 enhances by 5 Â 10 3 -10 6 -fold the susceptibility of the BALB/c3T3 and C3H10T1/2 mouse fibroblast lines to ultraviolet irradiation-as well as 3-methylcholanthrene-induced transformation. This result suggests that deregulated expression of Cdk6 and cyclinD3 may predispose cells to malignant transformation, supporting the recent finding that cyclin D3 activated by chromosomal rearrangement is the causative gene of non-Hodgkin B lymphoma, in which Cdk6 is the major partner kinase.

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“…For CDK6, this relates to the amplification and translocation of the relevant region of chromosome 7 (43)(44)(45)(46), and there is a single report of a sporadic mutation in a neuroblastoma that renders the protein insensitive to inhibition by p16…”

Section: Discussionmentioning

confidence: 99%

A CDKN2A Mutation in Familial Melanoma that Abrogates Binding of p16INK4a to CDK4 but not CDK6

et al. 2007

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The CDKN2A locus encodes two distinct proteins, p16 INK4a and p14 ARF , both of which are implicated in replicative senescence and tumor suppression in different contexts. Here, we describe the characterization of a novel strain of human diploid fibroblasts (designated Milan HDFs) from an individual who is homozygous for the R24P mutation in p16INK4a . As this mutation occurs in the first exon of INK4a (exon 1A), it has no effect on the primary sequence of p14 ARF . Based on both in vitro and in vivo analyses, the R24P variant is specifically defective for binding to CDK4 but remains able to associate with CDK6. Nevertheless, Milan HDFs behave as if they are p16INK4a deficient, in terms of sensitivity to spontaneous and oncogene-induced senescence, and the R24P variant has little effect on proliferation when ectopically expressed in normal fibroblasts. It can, however, impair the proliferation of U20S cells, presumably because they express more CDK6 than primary fibroblasts. These observations suggest that CDK4 and CDK6 are not functionally redundant and underscore the importance of CDK4 in the development of melanoma. [Cancer Res 2007;67(19):9134-41]

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Expression of Cyclin-Dependent Kinase 6 (cdk6) and Frequent Loss of CD44 in Nasal-Nasopharyngeal NK/T-Cell Lymphomas: Comparison with CD56-Negative Peripheral T-Cell Lymphomas

Cited by 31 publications

References 49 publications

Presence of Restricted Killer Immunoglobulin-Like Receptor Repertoire and Monoclonal T-Cell Receptor γ Rearrangement as Evidence of Mixed NK/T-Cell Differentiation in a Subset of Sinonasal Lymphomas

Presence of Restricted Killer Immunoglobulin-Like Receptor Repertoire and Monoclonal T-Cell Receptor γ Rearrangement as Evidence of Mixed NK/T-Cell Differentiation in a Subset of Sinonasal Lymphomas

Overexpression of Cdk6–cyclin D3 highly sensitizes cells to physical and chemical transformation

A CDKN2A Mutation in Familial Melanoma that Abrogates Binding of p16INK4a to CDK4 but not CDK6

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