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Article: 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

TitleNatural 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
Authors
Keywordsaurora kinase A
gene-expression signature
NOTCH pathway
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leu
Citation
Leukemia, 2011, v. 25 n. 2, p. 348-358 How to Cite?
AbstractNatural killer (NK) cell lymphomas/leukemias are rare neoplasms with an aggressive clinical behavior. The majority of the cases belong to extranodal NK/T-cell lymphoma, nasal type (ENKTL) in the current WHO classification scheme. Gene-expression profiling (GEP) of 21 ENKTL and NK-cell lymphoma/leukemia patients, 17 NK- and T-cell lines and 5 indolent NK-cell large-granular- lymphocytic proliferation was performed and compared with 125 peripheral T-cell lymphoma (PTCL) patients previously studied. The molecular classifier derived for ENKTL patients was comprised of 84 transcripts with the majority of them contributed by the neoplastic NK cells. The classifier also identified a set of γ-PTCLs both in the ENKTL cases as well as in cases initially classified as PTCL-not otherwise specified. These γ-PTCLs expressed transcripts associated with the T-cell receptor (TCR)/CD3 complex, suggesting T cell rather than NK-cell lineage. They were very similar to NK-cell tumors by GEP, but were distinct from cytotoxic (αΒ)-PTCL and hepatosplenic T-cell lymphoma, indicating derivation from an ontogenically and functionally distinct subset of γ T cells. They showed distinct expression of Vγ9, V2 transcripts and were positive for TCRγ, but negative for TCRΒ by immunohistochemistry. Targeted inhibition of two oncogenic pathways (AURKA and NOTCH-1) by small-molecular inhibitors induced significant growth arrest in NK-cell lines, thus providing a rationale for clinical trials of these inhibitors in NK-cell malignancies. © 2011 Macmillan Publishers Limited All rights reserved.
DescriptionPresented in part at the oral-session at the 51st American Society of Hematology (ASH) Annual Meeting, New Orleans, LA, 5–8 December 2009
Persistent Identifierhttp://hdl.handle.net/10722/139939
ISSN
2015 Impact Factor: 12.104
2015 SCImago Journal Rankings: 5.142
ISI Accession Number ID
Funding AgencyGrant Number
NCI5U01/CA114778
Lymphoma SPOREP50CA136411-01(NC1)
International Peripheral T-cell Lymphoma Project
Eppley Cancer InstituteCA36727
National Center for Research ResourcesP20 RR016469
Funding Information:

We thank Martin Bast for clinical data collection, and Kavita Patel and Lisa Bough for their technical assistance. This work was supported in part by NCI Grant 5U01/CA114778, Lymphoma SPORE P50CA136411-01(NC1) and funds from the International Peripheral T-cell Lymphoma Project and Eppley Cancer Institute Core Grant CA36727. The UNMC Microarray Core Facility is supported partially by NIH Grant P20 RR016469 from the INBRE Program of the National Center for Research Resources.

References

 

DC FieldValueLanguage
dc.contributor.authorIqbal, Jen_HK
dc.contributor.authorWeisenburger, DDen_HK
dc.contributor.authorChowdhury, Aen_HK
dc.contributor.authorTsai, MYen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorGreiner, TCen_HK
dc.contributor.authorKucuk, Cen_HK
dc.contributor.authorDeffenbacher, Ken_HK
dc.contributor.authorVose, Jen_HK
dc.contributor.authorSmith, Len_HK
dc.contributor.authorAu, WYen_HK
dc.contributor.authorNakamura, Sen_HK
dc.contributor.authorSeto, Men_HK
dc.contributor.authorDelabie, Jen_HK
dc.contributor.authorBerger, Fen_HK
dc.contributor.authorLoong, Fen_HK
dc.contributor.authorKo, YHen_HK
dc.contributor.authorSng, Ien_HK
dc.contributor.authorLiu, Xen_HK
dc.contributor.authorLoughran, TPen_HK
dc.contributor.authorArmitage, Jen_HK
dc.contributor.authorChan, WCen_HK
dc.date.accessioned2011-09-23T06:02:10Z-
dc.date.available2011-09-23T06:02:10Z-
dc.date.issued2011en_HK
dc.identifier.citationLeukemia, 2011, v. 25 n. 2, p. 348-358en_HK
dc.identifier.issn0887-6924en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139939-
dc.descriptionPresented in part at the oral-session at the 51st American Society of Hematology (ASH) Annual Meeting, New Orleans, LA, 5–8 December 2009-
dc.description.abstractNatural killer (NK) cell lymphomas/leukemias are rare neoplasms with an aggressive clinical behavior. The majority of the cases belong to extranodal NK/T-cell lymphoma, nasal type (ENKTL) in the current WHO classification scheme. Gene-expression profiling (GEP) of 21 ENKTL and NK-cell lymphoma/leukemia patients, 17 NK- and T-cell lines and 5 indolent NK-cell large-granular- lymphocytic proliferation was performed and compared with 125 peripheral T-cell lymphoma (PTCL) patients previously studied. The molecular classifier derived for ENKTL patients was comprised of 84 transcripts with the majority of them contributed by the neoplastic NK cells. The classifier also identified a set of γ-PTCLs both in the ENKTL cases as well as in cases initially classified as PTCL-not otherwise specified. These γ-PTCLs expressed transcripts associated with the T-cell receptor (TCR)/CD3 complex, suggesting T cell rather than NK-cell lineage. They were very similar to NK-cell tumors by GEP, but were distinct from cytotoxic (αΒ)-PTCL and hepatosplenic T-cell lymphoma, indicating derivation from an ontogenically and functionally distinct subset of γ T cells. They showed distinct expression of Vγ9, V2 transcripts and were positive for TCRγ, but negative for TCRΒ by immunohistochemistry. Targeted inhibition of two oncogenic pathways (AURKA and NOTCH-1) by small-molecular inhibitors induced significant growth arrest in NK-cell lines, thus providing a rationale for clinical trials of these inhibitors in NK-cell malignancies. © 2011 Macmillan Publishers Limited All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leuen_HK
dc.relation.ispartofLeukemiaen_HK
dc.subjectaurora kinase Aen_HK
dc.subjectgene-expression signatureen_HK
dc.subjectNOTCH pathwayen_HK
dc.subject.meshKiller Cells, Natural - pathology-
dc.subject.meshLymphoma, Non-Hodgkin - pathology-
dc.subject.meshLymphoma, T-Cell, Peripheral - pathology-
dc.subject.meshProtein-Serine-Threonine Kinases - antagonists and inhibitors-
dc.subject.meshReceptors, Antigen, T-Cell, gamma-delta-
dc.titleNatural 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 vitroen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0887-6924&volume=25&issue=2&spage=348&epage=358&date=2011&atitle=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-
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/leu.2010.255en_HK
dc.identifier.pmid21052088-
dc.identifier.scopuseid_2-s2.0-79751531010en_HK
dc.identifier.hkuros192573en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79751531010&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue2en_HK
dc.identifier.spage348en_HK
dc.identifier.epage358en_HK
dc.identifier.isiWOS:000287188600020-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.citeulike8210615-

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