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Polymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia

The P2X7 receptor is a ligand-gated cation channel that mediates ATP-induced apoptotic death in haemopoietic and chronic lymphocytic leukaemia (CLL) cells. We aimed to investigate the clinical effect of a single nucleotide polymorphism in the P2X7 receptor gene (1513A⇒C) and correlate findings with... Full description

Journal Title: The Lancet (British edition) 2002-12-14, Vol.360 (9349), p.1935-1939
Main Author: Thunberg, Ulf
Other Authors: Tobin, Gerard , Johnson, Anna , Söderberg, Ola , Padyukov, Leonid , Hultdin, Magnus , Klareskog, Lars , Enblad, Gunilla , Sundström, Christer , Roos, Göran , Rosenquist, Richard
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: London: Elsevier Ltd
ID: ISSN: 0140-6736
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title: Polymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia
format: Article
creator:
  • Thunberg, Ulf
  • Tobin, Gerard
  • Johnson, Anna
  • Söderberg, Ola
  • Padyukov, Leonid
  • Hultdin, Magnus
  • Klareskog, Lars
  • Enblad, Gunilla
  • Sundström, Christer
  • Roos, Göran
  • Rosenquist, Richard
subjects:
  • Abridged Index Medicus
  • Adenosine triphosphate
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Apoptosis
  • Biological and medical sciences
  • Cancer
  • Case-Control Studies
  • Cells
  • Chronic lymphatic leukemia
  • Chronic lymphocytic leukemia
  • Dendritic cells
  • Female
  • Gene polymorphism
  • Genes
  • Genetic aspects
  • Genetic polymorphisms
  • Genotype
  • Genotype & phenotype
  • Genotypes
  • Health aspects
  • Hematology
  • Humans
  • Immunoglobulins
  • Investigative techniques, diagnostic techniques (general aspects)
  • Ion channels
  • Laboratories
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell - genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell - mortality
  • Leukemia
  • Lymphocytic
  • Chronic/genetics/mortality
  • Lymphocytes
  • Male
  • Medical and Health Sciences
  • Medical prognosis
  • Medical research
  • Medical sciences
  • Medicin och hälsovetenskap
  • Middle Aged
  • Mortality
  • Mutation
  • Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
  • Patient outcomes
  • Patients
  • Point mutation
  • Polymerase chain reaction
  • Polymorphism
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Receptors, Purinergic P2 - genetics
  • Receptors, Purinergic P2X7
  • Restriction fragment length polymorphism
  • Single-nucleotide polymorphism
  • Spleen
  • Survival
  • Tumors
ispartof: The Lancet (British edition), 2002-12-14, Vol.360 (9349), p.1935-1939
description: The P2X7 receptor is a ligand-gated cation channel that mediates ATP-induced apoptotic death in haemopoietic and chronic lymphocytic leukaemia (CLL) cells. We aimed to investigate the clinical effect of a single nucleotide polymorphism in the P2X7 receptor gene (1513A⇒C) and correlate findings with the immunoglobulin heavy chain variable (VH) gene mutation status, a prognostic marker in CLL. We investigated tumour DMA in 170 patients with CLL using PCR-RFLP analysis with Hhal restriction enzyme cleavage to screen for the polymorphism in the P2X7 receptor gene. The VH gene mutation status was assessed in 165 patients by PCR amplification and nucleotide sequencing. We correlated the findings of the P2X7 receptor genotype with the VH gene mutation data and overall survival and screened for the P2X7 receptor polymorphism in 200 healthy controls. Of the 170 patients, 35 (21%) were heterozygous and one (1%) homozygous for the 1513C allele; whereas 134 (79%) had the 1513A/A genotype of the P2X7 receptor gene. Overall survival was significantly longer for patients with CLL heterozygous for the 1513C allele than those with the 1513A/A genotype. Median survival for heterozygous patients was 104 months (range 33–467) and 72 months (1–190) for homozygous patients (p=0·009). Of the 165 patients with CLL in whom we assessed the VH gene mutation status, the VH genes were mutated in 71 (43%) patients and unmutated in 94; 18 (25%) of the 71 patients with mutated genes had 1513C allele compared with 17 (18%) of 94 who had unmutated genes. In patients with mutated VH genes, those with CLL who were 1513C positive had 53 months' longer median survival than did those with the 1513A/A genotype (151 vs 98 months, p=0·011). The P2X7 polymorphism could affect clinical outcome in CLL, especially in patients with mutated VH genes. Studies are necessary to elucidate the biological role of the P2X7 polymorphism in CLL in vivo.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
  • 1474-547X
url: Link


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titlePolymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia
sourceAlma/SFX Local Collection
creatorThunberg, Ulf ; Tobin, Gerard ; Johnson, Anna ; Söderberg, Ola ; Padyukov, Leonid ; Hultdin, Magnus ; Klareskog, Lars ; Enblad, Gunilla ; Sundström, Christer ; Roos, Göran ; Rosenquist, Richard
creatorcontribThunberg, Ulf ; Tobin, Gerard ; Johnson, Anna ; Söderberg, Ola ; Padyukov, Leonid ; Hultdin, Magnus ; Klareskog, Lars ; Enblad, Gunilla ; Sundström, Christer ; Roos, Göran ; Rosenquist, Richard
descriptionThe P2X7 receptor is a ligand-gated cation channel that mediates ATP-induced apoptotic death in haemopoietic and chronic lymphocytic leukaemia (CLL) cells. We aimed to investigate the clinical effect of a single nucleotide polymorphism in the P2X7 receptor gene (1513A⇒C) and correlate findings with the immunoglobulin heavy chain variable (VH) gene mutation status, a prognostic marker in CLL. We investigated tumour DMA in 170 patients with CLL using PCR-RFLP analysis with Hhal restriction enzyme cleavage to screen for the polymorphism in the P2X7 receptor gene. The VH gene mutation status was assessed in 165 patients by PCR amplification and nucleotide sequencing. We correlated the findings of the P2X7 receptor genotype with the VH gene mutation data and overall survival and screened for the P2X7 receptor polymorphism in 200 healthy controls. Of the 170 patients, 35 (21%) were heterozygous and one (1%) homozygous for the 1513C allele; whereas 134 (79%) had the 1513A/A genotype of the P2X7 receptor gene. Overall survival was significantly longer for patients with CLL heterozygous for the 1513C allele than those with the 1513A/A genotype. Median survival for heterozygous patients was 104 months (range 33–467) and 72 months (1–190) for homozygous patients (p=0·009). Of the 165 patients with CLL in whom we assessed the VH gene mutation status, the VH genes were mutated in 71 (43%) patients and unmutated in 94; 18 (25%) of the 71 patients with mutated genes had 1513C allele compared with 17 (18%) of 94 who had unmutated genes. In patients with mutated VH genes, those with CLL who were 1513C positive had 53 months' longer median survival than did those with the 1513A/A genotype (151 vs 98 months, p=0·011). The P2X7 polymorphism could affect clinical outcome in CLL, especially in patients with mutated VH genes. Studies are necessary to elucidate the biological role of the P2X7 polymorphism in CLL in vivo.
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1ISSN: 1474-547X
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3DOI: 10.1016/S0140-6736(02)11917-9
4PMID: 12493261
5CODEN: LANCAO
languageeng
publisherLondon: Elsevier Ltd
subjectAbridged Index Medicus ; Adenosine triphosphate ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Apoptosis ; Biological and medical sciences ; Cancer ; Case-Control Studies ; Cells ; Chronic lymphatic leukemia ; Chronic lymphocytic leukemia ; Dendritic cells ; Female ; Gene polymorphism ; Genes ; Genetic aspects ; Genetic polymorphisms ; Genotype ; Genotype & phenotype ; Genotypes ; Health aspects ; Hematology ; Humans ; Immunoglobulins ; Investigative techniques, diagnostic techniques (general aspects) ; Ion channels ; Laboratories ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - mortality ; Leukemia; Lymphocytic; Chronic/genetics/mortality ; Lymphocytes ; Male ; Medical and Health Sciences ; Medical prognosis ; Medical research ; Medical sciences ; Medicin och hälsovetenskap ; Middle Aged ; Mortality ; Mutation ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Patient outcomes ; Patients ; Point mutation ; Polymerase chain reaction ; Polymorphism ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptors, Purinergic P2 - genetics ; Receptors, Purinergic P2X7 ; Restriction fragment length polymorphism ; Single-nucleotide polymorphism ; Spleen ; Survival ; Tumors
ispartofThe Lancet (British edition), 2002-12-14, Vol.360 (9349), p.1935-1939
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0Thunberg, Ulf
1Tobin, Gerard
2Johnson, Anna
3Söderberg, Ola
4Padyukov, Leonid
5Hultdin, Magnus
6Klareskog, Lars
7Enblad, Gunilla
8Sundström, Christer
9Roos, Göran
10Rosenquist, Richard
title
0Polymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia
1The Lancet (British edition)
addtitleLancet
descriptionThe P2X7 receptor is a ligand-gated cation channel that mediates ATP-induced apoptotic death in haemopoietic and chronic lymphocytic leukaemia (CLL) cells. We aimed to investigate the clinical effect of a single nucleotide polymorphism in the P2X7 receptor gene (1513A⇒C) and correlate findings with the immunoglobulin heavy chain variable (VH) gene mutation status, a prognostic marker in CLL. We investigated tumour DMA in 170 patients with CLL using PCR-RFLP analysis with Hhal restriction enzyme cleavage to screen for the polymorphism in the P2X7 receptor gene. The VH gene mutation status was assessed in 165 patients by PCR amplification and nucleotide sequencing. We correlated the findings of the P2X7 receptor genotype with the VH gene mutation data and overall survival and screened for the P2X7 receptor polymorphism in 200 healthy controls. Of the 170 patients, 35 (21%) were heterozygous and one (1%) homozygous for the 1513C allele; whereas 134 (79%) had the 1513A/A genotype of the P2X7 receptor gene. Overall survival was significantly longer for patients with CLL heterozygous for the 1513C allele than those with the 1513A/A genotype. Median survival for heterozygous patients was 104 months (range 33–467) and 72 months (1–190) for homozygous patients (p=0·009). Of the 165 patients with CLL in whom we assessed the VH gene mutation status, the VH genes were mutated in 71 (43%) patients and unmutated in 94; 18 (25%) of the 71 patients with mutated genes had 1513C allele compared with 17 (18%) of 94 who had unmutated genes. In patients with mutated VH genes, those with CLL who were 1513C positive had 53 months' longer median survival than did those with the 1513A/A genotype (151 vs 98 months, p=0·011). The P2X7 polymorphism could affect clinical outcome in CLL, especially in patients with mutated VH genes. Studies are necessary to elucidate the biological role of the P2X7 polymorphism in CLL in vivo.
subject
0Abridged Index Medicus
1Adenosine triphosphate
2Adult
3Aged
4Aged, 80 and over
5Alleles
6Apoptosis
7Biological and medical sciences
8Cancer
9Case-Control Studies
10Cells
11Chronic lymphatic leukemia
12Chronic lymphocytic leukemia
13Dendritic cells
14Female
15Gene polymorphism
16Genes
17Genetic aspects
18Genetic polymorphisms
19Genotype
20Genotype & phenotype
21Genotypes
22Health aspects
23Hematology
24Humans
25Immunoglobulins
26Investigative techniques, diagnostic techniques (general aspects)
27Ion channels
28Laboratories
29Leukemia
30Leukemia, Lymphocytic, Chronic, B-Cell - genetics
31Leukemia, Lymphocytic, Chronic, B-Cell - mortality
32Leukemia; Lymphocytic; Chronic/genetics/mortality
33Lymphocytes
34Male
35Medical and Health Sciences
36Medical prognosis
37Medical research
38Medical sciences
39Medicin och hälsovetenskap
40Middle Aged
41Mortality
42Mutation
43Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
44Patient outcomes
45Patients
46Point mutation
47Polymerase chain reaction
48Polymorphism
49Polymorphism, Genetic
50Polymorphism, Restriction Fragment Length
51Receptors, Purinergic P2 - genetics
52Receptors, Purinergic P2X7
53Restriction fragment length polymorphism
54Single-nucleotide polymorphism
55Spleen
56Survival
57Tumors
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6Klareskog, Lars
7Enblad, Gunilla
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titlePolymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia
authorThunberg, Ulf ; Tobin, Gerard ; Johnson, Anna ; Söderberg, Ola ; Padyukov, Leonid ; Hultdin, Magnus ; Klareskog, Lars ; Enblad, Gunilla ; Sundström, Christer ; Roos, Göran ; Rosenquist, Richard
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1Adenosine triphosphate
2Adult
3Aged
4Aged, 80 and over
5Alleles
6Apoptosis
7Biological and medical sciences
8Cancer
9Case-Control Studies
10Cells
11Chronic lymphatic leukemia
12Chronic lymphocytic leukemia
13Dendritic cells
14Female
15Gene polymorphism
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18Genetic polymorphisms
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20Genotype & phenotype
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25Immunoglobulins
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35Medical and Health Sciences
36Medical prognosis
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39Medicin och hälsovetenskap
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42Mutation
43Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
44Patient outcomes
45Patients
46Point mutation
47Polymerase chain reaction
48Polymorphism
49Polymorphism, Genetic
50Polymorphism, Restriction Fragment Length
51Receptors, Purinergic P2 - genetics
52Receptors, Purinergic P2X7
53Restriction fragment length polymorphism
54Single-nucleotide polymorphism
55Spleen
56Survival
57Tumors
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jtitleThe Lancet (British edition)
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abstractThe P2X7 receptor is a ligand-gated cation channel that mediates ATP-induced apoptotic death in haemopoietic and chronic lymphocytic leukaemia (CLL) cells. We aimed to investigate the clinical effect of a single nucleotide polymorphism in the P2X7 receptor gene (1513A⇒C) and correlate findings with the immunoglobulin heavy chain variable (VH) gene mutation status, a prognostic marker in CLL. We investigated tumour DMA in 170 patients with CLL using PCR-RFLP analysis with Hhal restriction enzyme cleavage to screen for the polymorphism in the P2X7 receptor gene. The VH gene mutation status was assessed in 165 patients by PCR amplification and nucleotide sequencing. We correlated the findings of the P2X7 receptor genotype with the VH gene mutation data and overall survival and screened for the P2X7 receptor polymorphism in 200 healthy controls. Of the 170 patients, 35 (21%) were heterozygous and one (1%) homozygous for the 1513C allele; whereas 134 (79%) had the 1513A/A genotype of the P2X7 receptor gene. Overall survival was significantly longer for patients with CLL heterozygous for the 1513C allele than those with the 1513A/A genotype. Median survival for heterozygous patients was 104 months (range 33–467) and 72 months (1–190) for homozygous patients (p=0·009). Of the 165 patients with CLL in whom we assessed the VH gene mutation status, the VH genes were mutated in 71 (43%) patients and unmutated in 94; 18 (25%) of the 71 patients with mutated genes had 1513C allele compared with 17 (18%) of 94 who had unmutated genes. In patients with mutated VH genes, those with CLL who were 1513C positive had 53 months' longer median survival than did those with the 1513A/A genotype (151 vs 98 months, p=0·011). The P2X7 polymorphism could affect clinical outcome in CLL, especially in patients with mutated VH genes. Studies are necessary to elucidate the biological role of the P2X7 polymorphism in CLL in vivo.
copLondon
pubElsevier Ltd
pmid12493261
doi10.1016/S0140-6736(02)11917-9