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The HLA-B-21 dimorp...
The HLA-B-21 dimorphism impacts on NK cell education and clinical outcome of immunotherapy in acute myeloid leukemia
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- Hallner, Alexander, 1990 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Bernson, Elin, 1987 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Hussein, Brwa Ali, 1984 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Sander, Frida Ewald (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Brune, Mats, 1950 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine
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- Aurelius, Johan, 1980 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Martner, Anna, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Hellstrand, Kristoffer, 1956 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Bergh Thorén, Fredrik, 1976 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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(creator_code:org_t)
- American Society of Hematology, 2019
- 2019
- Engelska.
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 133:13, s. 1479-1488
- Relaterad länk:
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https://ashpublicati...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Natural killer (NK) cell function is regulated by inhibitory receptors, such as the family of killer immunoglobulin-like receptors (KIRs) and the NKG2A/CD94 heterodimer. These receptors recognize cognate HLA class I molecules on potential target cells, and recent studies imply that an HLA-B dimorphism at position -21 in the gene segment encoding the leader peptide dictates whether NK cell regulation primarily relies on the KIRs or the NKG2A/CD94 receptor. The impact of this HLA-B dimorphism on NK cell-mediated destruction of leukemic cells or on the course of leukemia is largely unknown. In a first part of this study, we compared functions of NK cells in subjects carrying HLA-B -21Mor 21T using interleukin-2 (IL-2)-activated NK cells and leukemic cells from patients with acute myeloid leukemia (AML). Subjects carrying HLA-B -21M harbored better-educated NKG2A1 NK cells and displayed superior capacity to degranulate lytic granules against KIR ligandmatched primary leukemic blasts. Second, we aimed to define the potential impact of HLA-B -21 variation on the course of AML in a phase 4 trial in which patients received IL-2based immunotherapy. In keeping with the hypothesis that 21M may be associated with improved NK cell functionality, we observed superior leukemia-free survival and overall survival in -21M patients than in -21T patients during IL-2based immunotherapy. We propose that genetic variation at HLA-B -21 may determine the antileukemic efficacy of activated NK cells and the clinical benefit of NK cell-activating immunotherapy.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- mhc class-i
- natural-killer-cells
- hla-c expression
- inhibitory
- receptors
- activation
- relapse
- association
- cd94/nkg2a
- molecules
- infection
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Blood
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Hallner, Alexand ...
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Bernson, Elin, 1 ...
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Hussein, Brwa Al ...
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Sander, Frida Ew ...
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Brune, Mats, 195 ...
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Aurelius, Johan, ...
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Martner, Anna, 1 ...
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Hellstrand, Kris ...
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Bergh Thorén, Fr ...
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Göteborgs universitet