TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis
High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL -negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an o...
Gespeichert in:
| Veröffentlicht in: | Leukemia 2009-05, Vol.23 (5), p.905-911 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 911 |
|---|---|
| container_issue | 5 |
| container_start_page | 905 |
| container_title | Leukemia |
| container_volume | 23 |
| creator | Tefferi, A Pardanani, A Lim, K-H Abdel-Wahab, O Lasho, T L Patel, J Gangat, N Finke, C M Schwager, S Mullally, A Li, C-Y Hanson, C A Mesa, R Bernard, O Delhommeau, F Vainchenker, W Gilliland, D G Levine, R L |
| description | High-throughput DNA sequence analysis was used to screen for
TET2
mutations in bone marrow-derived DNA from 239 patients with
BCR-ABL
-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of ∼13%. Specific diagnoses included polycythemia vera (PV;
n
=89), essential thrombocythemia (ET;
n
=57), primary myelofibrosis (PMF;
n
=60), post-PV MF (
n
=14), post-ET MF (
n
=7) and blast phase PV/ET/MF (
n
=12); the corresponding mutational frequencies were ∼16, 5, 17, 14, 14 and 17% (
P
=0.50). Mutant
TET2
was detected in ∼17 and ∼7% of
JAK2
V617F-positive and -negative cases, respectively (
P
=0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant
TET2
and advanced age; mutational frequency was ∼23% in patients ⩾60 years old versus ∼4% in younger patients (
P |
| doi_str_mv | 10.1038/leu.2009.47 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4654629</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A201865932</galeid><sourcerecordid>A201865932</sourcerecordid><originalsourceid>FETCH-LOGICAL-c631t-5d96522deebdfab72999434eecefdd5cb5f01e69aca3fc9c463f81ac031165ad3</originalsourceid><addsrcrecordid>eNp9kk1vEzEQhlcIREPhxB2tQJQDTbC9tnd9Qaqq8iFV4hLOltc7Tlx57WDvVsq_x0uipEEF-WDJ88w745m3KF5jtMCoaj45GBcEIbGg9ZNihmnN54wx_LSYoaap51wQela8SOkOoSnInxdnWBBOOMKzwi9vlqTsx0ENNvhUKt-VwxpsLLWz3mrlSh1iBKcGSKX15Sa4rd5mpLeqvIeoLktICfxgMzqsY-jbcIhPav0WXDC2jSHZ9LJ4ZpRL8Gp_nxc_v9wsr7_Nb398_X59dTvXvMLDnHWCM0I6gLYzqq2JEIJWFECD6TqmW2YQBi6UVpXRQlNemQYrjSqMOVNddV583uluxraHTuf-onJyE22v4lYGZeVpxNu1XIV7STmjnIgs8GEvEMOvEdIge5s0OKc8hDHJmtGmYTXimbz4L8lrQhitmgy--wu8C2P0eQyScMpq0lA6yb39J0UQo0iQ-ii1Ug6k9SbkT-iprrwiCDeciYpkavEIlU-Xl6ODB2Pz-0nCxYOENSg3rFNw4x9rnIIfd6DOW00RzGGyGMnJlDKbUk6mlHTq9s3DZRzZvQsz8H4PqJQdZ6Ly2qYDRzCrGsFY5i53XMohv4J4nM1jdX8Daaz4_w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>220540927</pqid></control><display><type>article</type><title>TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature Journals Online</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Tefferi, A ; Pardanani, A ; Lim, K-H ; Abdel-Wahab, O ; Lasho, T L ; Patel, J ; Gangat, N ; Finke, C M ; Schwager, S ; Mullally, A ; Li, C-Y ; Hanson, C A ; Mesa, R ; Bernard, O ; Delhommeau, F ; Vainchenker, W ; Gilliland, D G ; Levine, R L</creator><creatorcontrib>Tefferi, A ; Pardanani, A ; Lim, K-H ; Abdel-Wahab, O ; Lasho, T L ; Patel, J ; Gangat, N ; Finke, C M ; Schwager, S ; Mullally, A ; Li, C-Y ; Hanson, C A ; Mesa, R ; Bernard, O ; Delhommeau, F ; Vainchenker, W ; Gilliland, D G ; Levine, R L</creatorcontrib><description>High-throughput DNA sequence analysis was used to screen for
TET2
mutations in bone marrow-derived DNA from 239 patients with
BCR-ABL
-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of ∼13%. Specific diagnoses included polycythemia vera (PV;
n
=89), essential thrombocythemia (ET;
n
=57), primary myelofibrosis (PMF;
n
=60), post-PV MF (
n
=14), post-ET MF (
n
=7) and blast phase PV/ET/MF (
n
=12); the corresponding mutational frequencies were ∼16, 5, 17, 14, 14 and 17% (
P
=0.50). Mutant
TET2
was detected in ∼17 and ∼7% of
JAK2
V617F-positive and -negative cases, respectively (
P
=0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant
TET2
and advanced age; mutational frequency was ∼23% in patients ⩾60 years old versus ∼4% in younger patients (
P
<0.0001). The presence of mutant
TET2
did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted (
P
=0.05). We conclude that
TET2
mutations occur in both
JAK2
V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2009.47</identifier><identifier>PMID: 19262601</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Aged ; Aged, 80 and over ; BCR-ABL protein ; Biological and medical sciences ; Blood cancer ; Bone marrow ; Cancer ; Cancer Research ; Clustering ; Critical Care Medicine ; Deoxyribonucleic acid ; Disease ; Diseases of red blood cells ; DNA ; DNA-Binding Proteins - genetics ; Exons ; Female ; Frameshift mutation ; Fusion protein ; Gene mutations ; Genetic aspects ; Health aspects ; Hematologic and hematopoietic diseases ; Hematology ; Hemoglobin ; Humans ; Intensive ; Internal Medicine ; Janus Kinase 2 - genetics ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical prognosis ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Mutants ; Mutation ; Mutation - genetics ; Myelofibrosis ; Neoplasms ; Nucleotide sequence ; Oncology ; original-article ; Pathogenesis ; Patients ; Polycythemia ; Polycythemia vera ; Polycythemia Vera - genetics ; Polycythemias ; Primary Myelofibrosis - genetics ; Proto-Oncogene Proteins - genetics ; Risk factors ; Sequence analysis ; Stem cells ; Survival Rate ; Thrombocythemia ; Thrombocythemia, Essential - genetics ; Thrombocytosis ; Thromboembolism ; Thrombosis ; Tumors</subject><ispartof>Leukemia, 2009-05, Vol.23 (5), p.905-911</ispartof><rights>Macmillan Publishers Limited 2009</rights><rights>2009 INIST-CNRS</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2009</rights><rights>Macmillan Publishers Limited 2009.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c631t-5d96522deebdfab72999434eecefdd5cb5f01e69aca3fc9c463f81ac031165ad3</citedby><cites>FETCH-LOGICAL-c631t-5d96522deebdfab72999434eecefdd5cb5f01e69aca3fc9c463f81ac031165ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2009.47$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2009.47$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21538955$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19262601$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tefferi, A</creatorcontrib><creatorcontrib>Pardanani, A</creatorcontrib><creatorcontrib>Lim, K-H</creatorcontrib><creatorcontrib>Abdel-Wahab, O</creatorcontrib><creatorcontrib>Lasho, T L</creatorcontrib><creatorcontrib>Patel, J</creatorcontrib><creatorcontrib>Gangat, N</creatorcontrib><creatorcontrib>Finke, C M</creatorcontrib><creatorcontrib>Schwager, S</creatorcontrib><creatorcontrib>Mullally, A</creatorcontrib><creatorcontrib>Li, C-Y</creatorcontrib><creatorcontrib>Hanson, C A</creatorcontrib><creatorcontrib>Mesa, R</creatorcontrib><creatorcontrib>Bernard, O</creatorcontrib><creatorcontrib>Delhommeau, F</creatorcontrib><creatorcontrib>Vainchenker, W</creatorcontrib><creatorcontrib>Gilliland, D G</creatorcontrib><creatorcontrib>Levine, R L</creatorcontrib><title>TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>High-throughput DNA sequence analysis was used to screen for
TET2
mutations in bone marrow-derived DNA from 239 patients with
BCR-ABL
-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of ∼13%. Specific diagnoses included polycythemia vera (PV;
n
=89), essential thrombocythemia (ET;
n
=57), primary myelofibrosis (PMF;
n
=60), post-PV MF (
n
=14), post-ET MF (
n
=7) and blast phase PV/ET/MF (
n
=12); the corresponding mutational frequencies were ∼16, 5, 17, 14, 14 and 17% (
P
=0.50). Mutant
TET2
was detected in ∼17 and ∼7% of
JAK2
V617F-positive and -negative cases, respectively (
P
=0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant
TET2
and advanced age; mutational frequency was ∼23% in patients ⩾60 years old versus ∼4% in younger patients (
P
<0.0001). The presence of mutant
TET2
did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted (
P
=0.05). We conclude that
TET2
mutations occur in both
JAK2
V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>BCR-ABL protein</subject><subject>Biological and medical sciences</subject><subject>Blood cancer</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Clustering</subject><subject>Critical Care Medicine</subject><subject>Deoxyribonucleic acid</subject><subject>Disease</subject><subject>Diseases of red blood cells</subject><subject>DNA</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Exons</subject><subject>Female</subject><subject>Frameshift mutation</subject><subject>Fusion protein</subject><subject>Gene mutations</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Janus Kinase 2 - genetics</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Myelofibrosis</subject><subject>Neoplasms</subject><subject>Nucleotide sequence</subject><subject>Oncology</subject><subject>original-article</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Polycythemia</subject><subject>Polycythemia vera</subject><subject>Polycythemia Vera - genetics</subject><subject>Polycythemias</subject><subject>Primary Myelofibrosis - genetics</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Risk factors</subject><subject>Sequence analysis</subject><subject>Stem cells</subject><subject>Survival Rate</subject><subject>Thrombocythemia</subject><subject>Thrombocythemia, Essential - genetics</subject><subject>Thrombocytosis</subject><subject>Thromboembolism</subject><subject>Thrombosis</subject><subject>Tumors</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kk1vEzEQhlcIREPhxB2tQJQDTbC9tnd9Qaqq8iFV4hLOltc7Tlx57WDvVsq_x0uipEEF-WDJ88w745m3KF5jtMCoaj45GBcEIbGg9ZNihmnN54wx_LSYoaap51wQela8SOkOoSnInxdnWBBOOMKzwi9vlqTsx0ENNvhUKt-VwxpsLLWz3mrlSh1iBKcGSKX15Sa4rd5mpLeqvIeoLktICfxgMzqsY-jbcIhPav0WXDC2jSHZ9LJ4ZpRL8Gp_nxc_v9wsr7_Nb398_X59dTvXvMLDnHWCM0I6gLYzqq2JEIJWFECD6TqmW2YQBi6UVpXRQlNemQYrjSqMOVNddV583uluxraHTuf-onJyE22v4lYGZeVpxNu1XIV7STmjnIgs8GEvEMOvEdIge5s0OKc8hDHJmtGmYTXimbz4L8lrQhitmgy--wu8C2P0eQyScMpq0lA6yb39J0UQo0iQ-ii1Ug6k9SbkT-iprrwiCDeciYpkavEIlU-Xl6ODB2Pz-0nCxYOENSg3rFNw4x9rnIIfd6DOW00RzGGyGMnJlDKbUk6mlHTq9s3DZRzZvQsz8H4PqJQdZ6Ly2qYDRzCrGsFY5i53XMohv4J4nM1jdX8Daaz4_w</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Tefferi, A</creator><creator>Pardanani, A</creator><creator>Lim, K-H</creator><creator>Abdel-Wahab, O</creator><creator>Lasho, T L</creator><creator>Patel, J</creator><creator>Gangat, N</creator><creator>Finke, C M</creator><creator>Schwager, S</creator><creator>Mullally, A</creator><creator>Li, C-Y</creator><creator>Hanson, C A</creator><creator>Mesa, R</creator><creator>Bernard, O</creator><creator>Delhommeau, F</creator><creator>Vainchenker, W</creator><creator>Gilliland, D G</creator><creator>Levine, R L</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090501</creationdate><title>TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis</title><author>Tefferi, A ; Pardanani, A ; Lim, K-H ; Abdel-Wahab, O ; Lasho, T L ; Patel, J ; Gangat, N ; Finke, C M ; Schwager, S ; Mullally, A ; Li, C-Y ; Hanson, C A ; Mesa, R ; Bernard, O ; Delhommeau, F ; Vainchenker, W ; Gilliland, D G ; Levine, R L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c631t-5d96522deebdfab72999434eecefdd5cb5f01e69aca3fc9c463f81ac031165ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>BCR-ABL protein</topic><topic>Biological and medical sciences</topic><topic>Blood cancer</topic><topic>Bone marrow</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Clustering</topic><topic>Critical Care Medicine</topic><topic>Deoxyribonucleic acid</topic><topic>Disease</topic><topic>Diseases of red blood cells</topic><topic>DNA</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Exons</topic><topic>Female</topic><topic>Frameshift mutation</topic><topic>Fusion protein</topic><topic>Gene mutations</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Janus Kinase 2 - genetics</topic><topic>Leukemia</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Myelofibrosis</topic><topic>Neoplasms</topic><topic>Nucleotide sequence</topic><topic>Oncology</topic><topic>original-article</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Polycythemia</topic><topic>Polycythemia vera</topic><topic>Polycythemia Vera - genetics</topic><topic>Polycythemias</topic><topic>Primary Myelofibrosis - genetics</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Risk factors</topic><topic>Sequence analysis</topic><topic>Stem cells</topic><topic>Survival Rate</topic><topic>Thrombocythemia</topic><topic>Thrombocythemia, Essential - genetics</topic><topic>Thrombocytosis</topic><topic>Thromboembolism</topic><topic>Thrombosis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tefferi, A</creatorcontrib><creatorcontrib>Pardanani, A</creatorcontrib><creatorcontrib>Lim, K-H</creatorcontrib><creatorcontrib>Abdel-Wahab, O</creatorcontrib><creatorcontrib>Lasho, T L</creatorcontrib><creatorcontrib>Patel, J</creatorcontrib><creatorcontrib>Gangat, N</creatorcontrib><creatorcontrib>Finke, C M</creatorcontrib><creatorcontrib>Schwager, S</creatorcontrib><creatorcontrib>Mullally, A</creatorcontrib><creatorcontrib>Li, C-Y</creatorcontrib><creatorcontrib>Hanson, C A</creatorcontrib><creatorcontrib>Mesa, R</creatorcontrib><creatorcontrib>Bernard, O</creatorcontrib><creatorcontrib>Delhommeau, F</creatorcontrib><creatorcontrib>Vainchenker, W</creatorcontrib><creatorcontrib>Gilliland, D G</creatorcontrib><creatorcontrib>Levine, R L</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tefferi, A</au><au>Pardanani, A</au><au>Lim, K-H</au><au>Abdel-Wahab, O</au><au>Lasho, T L</au><au>Patel, J</au><au>Gangat, N</au><au>Finke, C M</au><au>Schwager, S</au><au>Mullally, A</au><au>Li, C-Y</au><au>Hanson, C A</au><au>Mesa, R</au><au>Bernard, O</au><au>Delhommeau, F</au><au>Vainchenker, W</au><au>Gilliland, D G</au><au>Levine, R L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2009-05-01</date><risdate>2009</risdate><volume>23</volume><issue>5</issue><spage>905</spage><epage>911</epage><pages>905-911</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>High-throughput DNA sequence analysis was used to screen for
TET2
mutations in bone marrow-derived DNA from 239 patients with
BCR-ABL
-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of ∼13%. Specific diagnoses included polycythemia vera (PV;
n
=89), essential thrombocythemia (ET;
n
=57), primary myelofibrosis (PMF;
n
=60), post-PV MF (
n
=14), post-ET MF (
n
=7) and blast phase PV/ET/MF (
n
=12); the corresponding mutational frequencies were ∼16, 5, 17, 14, 14 and 17% (
P
=0.50). Mutant
TET2
was detected in ∼17 and ∼7% of
JAK2
V617F-positive and -negative cases, respectively (
P
=0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant
TET2
and advanced age; mutational frequency was ∼23% in patients ⩾60 years old versus ∼4% in younger patients (
P
<0.0001). The presence of mutant
TET2
did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted (
P
=0.05). We conclude that
TET2
mutations occur in both
JAK2
V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19262601</pmid><doi>10.1038/leu.2009.47</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2009-05, Vol.23 (5), p.905-911 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4654629 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Aged Aged, 80 and over BCR-ABL protein Biological and medical sciences Blood cancer Bone marrow Cancer Cancer Research Clustering Critical Care Medicine Deoxyribonucleic acid Disease Diseases of red blood cells DNA DNA-Binding Proteins - genetics Exons Female Frameshift mutation Fusion protein Gene mutations Genetic aspects Health aspects Hematologic and hematopoietic diseases Hematology Hemoglobin Humans Intensive Internal Medicine Janus Kinase 2 - genetics Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical prognosis Medical sciences Medicine Medicine & Public Health Middle Aged Mutants Mutation Mutation - genetics Myelofibrosis Neoplasms Nucleotide sequence Oncology original-article Pathogenesis Patients Polycythemia Polycythemia vera Polycythemia Vera - genetics Polycythemias Primary Myelofibrosis - genetics Proto-Oncogene Proteins - genetics Risk factors Sequence analysis Stem cells Survival Rate Thrombocythemia Thrombocythemia, Essential - genetics Thrombocytosis Thromboembolism Thrombosis Tumors |
| title | TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T09%3A43%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=TET2%20mutations%20and%20their%20clinical%20correlates%20in%20polycythemia%20vera,%20essential%20thrombocythemia%20and%20myelofibrosis&rft.jtitle=Leukemia&rft.au=Tefferi,%20A&rft.date=2009-05-01&rft.volume=23&rft.issue=5&rft.spage=905&rft.epage=911&rft.pages=905-911&rft.issn=0887-6924&rft.eissn=1476-5551&rft.coden=LEUKED&rft_id=info:doi/10.1038/leu.2009.47&rft_dat=%3Cgale_pubme%3EA201865932%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=220540927&rft_id=info:pmid/19262601&rft_galeid=A201865932&rfr_iscdi=true |