Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia
Calreticulin ( CALR ) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patient...
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| Veröffentlicht in: | Annals of hematology 2014-12, Vol.93 (12), p.2029-2036 |
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| creator | Chen, Chih-Cheng Gau, Jyh-Pyng Chou, Hui-Ju You, Jie-Yu Huang, Cih-En Chen, Yi-Yang Lung, Jrhau Chou, Yi-Sheng Leu, Yu-Wei Lu, Chang-Hsien Lee, Kuan-Der Tsai, Ying-Huang |
| description | Calreticulin (
CALR
) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of
JAK2
and
MPL
mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients,
CALR
mutations were detected in 33 (22.5 %),
JAK2
V617F in 94 (63.9 %), and
MPL
mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (
CALR
,
JAK2
V617F, and
MPL
; triple negative). Interestingly, one patient with the type 2
CALR
mutation also harbored a low allele burden (0.025 %) of
JAK2
V617F mutation. Furthermore, we found a novel
CALR
mutation, with the resultant protein sharing an identical amino acid sequence to the type 6
CALR
mutant. Compared to those with
JAK2
mutation,
CALR-
mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis.
CARL
mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in
JAK2
-mutated ET and PV patients. Multivariate analysis confirmed that younger age ( |
| doi_str_mv | 10.1007/s00277-014-2151-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1620537561</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3483166861</sourcerecordid><originalsourceid>FETCH-LOGICAL-c508t-921cbd47df5a2c8d9429d0ffe4cc881226014d8fd762b545e560fc5fb5ebb8b83</originalsourceid><addsrcrecordid>eNp1kM1uGyEUhVGVqHaTPkA3EVK2JbngYYZZWlHTNokUqWrWiOGnxvKAA4wUv31x7UbZhA3insN3dA9CXyhcUYDuOgOwriNAG8Iop0R8QHPaLBgBLpoTNId-0RNezwx9ynkNQJlo2Ec0YxwoB87m6OU22efJBu1t_or1xgev1QbrlUpKF5t8Ll5XRQWD41R0HC2ODuc4qirgm-XDLzxOpT5iyNgHfLe8Z2QK_2bWYJuzDcVXZFmlOA5R78rKjl6do1OnNtl-Pt5n6On22--bH-Th8fvPiiWagyikZ1QPpumM44ppYfqG9Qacs43WQlDG2rq9Ec50LRt4wy1vwWnuBm6HQQxicYYuD9xtinXRXOQ6TinUSElbBnzR8ZZWFz24dIo5J-vkNvlRpZ2kIPddy0PXsqbJfddyT744kqdhtOb1x_9yq4EdDLlK4Y9Nb6Lfpf4FnuCLNA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1620537561</pqid></control><display><type>article</type><title>Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Chen, Chih-Cheng ; Gau, Jyh-Pyng ; Chou, Hui-Ju ; You, Jie-Yu ; Huang, Cih-En ; Chen, Yi-Yang ; Lung, Jrhau ; Chou, Yi-Sheng ; Leu, Yu-Wei ; Lu, Chang-Hsien ; Lee, Kuan-Der ; Tsai, Ying-Huang</creator><creatorcontrib>Chen, Chih-Cheng ; Gau, Jyh-Pyng ; Chou, Hui-Ju ; You, Jie-Yu ; Huang, Cih-En ; Chen, Yi-Yang ; Lung, Jrhau ; Chou, Yi-Sheng ; Leu, Yu-Wei ; Lu, Chang-Hsien ; Lee, Kuan-Der ; Tsai, Ying-Huang</creatorcontrib><description>Calreticulin (
CALR
) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of
JAK2
and
MPL
mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients,
CALR
mutations were detected in 33 (22.5 %),
JAK2
V617F in 94 (63.9 %), and
MPL
mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (
CALR
,
JAK2
V617F, and
MPL
; triple negative). Interestingly, one patient with the type 2
CALR
mutation also harbored a low allele burden (0.025 %) of
JAK2
V617F mutation. Furthermore, we found a novel
CALR
mutation, with the resultant protein sharing an identical amino acid sequence to the type 6
CALR
mutant. Compared to those with
JAK2
mutation,
CALR-
mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis.
CARL
mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in
JAK2
-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of
CALR
mutations, and a lower platelet count (<1,000 × 10
9
/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that
CALR
mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.</description><identifier>ISSN: 0939-5555</identifier><identifier>EISSN: 1432-0584</identifier><identifier>DOI: 10.1007/s00277-014-2151-8</identifier><identifier>PMID: 25015052</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Amino Acid Sequence ; Calreticulin - genetics ; Female ; Hematology ; Humans ; Janus Kinase 2 - genetics ; Kaplan-Meier Estimate ; Leukocyte Count ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Molecular Sequence Data ; Mutation ; Oncology ; Original Article ; Phenotype ; Platelet Count ; Proportional Hazards Models ; Receptors, Thrombopoietin - genetics ; Sequence Alignment ; Sequence Deletion ; Sequence Homology, Amino Acid ; Splenomegaly - etiology ; Taiwan - epidemiology ; Thrombocythemia, Essential - complications ; Thrombocythemia, Essential - ethnology ; Thrombocythemia, Essential - genetics ; Thrombocythemia, Essential - mortality ; Thrombophilia - etiology ; Young Adult</subject><ispartof>Annals of hematology, 2014-12, Vol.93 (12), p.2029-2036</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-921cbd47df5a2c8d9429d0ffe4cc881226014d8fd762b545e560fc5fb5ebb8b83</citedby><cites>FETCH-LOGICAL-c508t-921cbd47df5a2c8d9429d0ffe4cc881226014d8fd762b545e560fc5fb5ebb8b83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00277-014-2151-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00277-014-2151-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25015052$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Chih-Cheng</creatorcontrib><creatorcontrib>Gau, Jyh-Pyng</creatorcontrib><creatorcontrib>Chou, Hui-Ju</creatorcontrib><creatorcontrib>You, Jie-Yu</creatorcontrib><creatorcontrib>Huang, Cih-En</creatorcontrib><creatorcontrib>Chen, Yi-Yang</creatorcontrib><creatorcontrib>Lung, Jrhau</creatorcontrib><creatorcontrib>Chou, Yi-Sheng</creatorcontrib><creatorcontrib>Leu, Yu-Wei</creatorcontrib><creatorcontrib>Lu, Chang-Hsien</creatorcontrib><creatorcontrib>Lee, Kuan-Der</creatorcontrib><creatorcontrib>Tsai, Ying-Huang</creatorcontrib><title>Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia</title><title>Annals of hematology</title><addtitle>Ann Hematol</addtitle><addtitle>Ann Hematol</addtitle><description>Calreticulin (
CALR
) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of
JAK2
and
MPL
mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients,
CALR
mutations were detected in 33 (22.5 %),
JAK2
V617F in 94 (63.9 %), and
MPL
mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (
CALR
,
JAK2
V617F, and
MPL
; triple negative). Interestingly, one patient with the type 2
CALR
mutation also harbored a low allele burden (0.025 %) of
JAK2
V617F mutation. Furthermore, we found a novel
CALR
mutation, with the resultant protein sharing an identical amino acid sequence to the type 6
CALR
mutant. Compared to those with
JAK2
mutation,
CALR-
mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis.
CARL
mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in
JAK2
-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of
CALR
mutations, and a lower platelet count (<1,000 × 10
9
/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that
CALR
mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.</description><subject>Adult</subject><subject>Age Distribution</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amino Acid Sequence</subject><subject>Calreticulin - genetics</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Janus Kinase 2 - genetics</subject><subject>Kaplan-Meier Estimate</subject><subject>Leukocyte Count</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Phenotype</subject><subject>Platelet Count</subject><subject>Proportional Hazards Models</subject><subject>Receptors, Thrombopoietin - genetics</subject><subject>Sequence Alignment</subject><subject>Sequence Deletion</subject><subject>Sequence Homology, Amino Acid</subject><subject>Splenomegaly - etiology</subject><subject>Taiwan - epidemiology</subject><subject>Thrombocythemia, Essential - complications</subject><subject>Thrombocythemia, Essential - ethnology</subject><subject>Thrombocythemia, Essential - genetics</subject><subject>Thrombocythemia, Essential - mortality</subject><subject>Thrombophilia - etiology</subject><subject>Young Adult</subject><issn>0939-5555</issn><issn>1432-0584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kM1uGyEUhVGVqHaTPkA3EVK2JbngYYZZWlHTNokUqWrWiOGnxvKAA4wUv31x7UbZhA3insN3dA9CXyhcUYDuOgOwriNAG8Iop0R8QHPaLBgBLpoTNId-0RNezwx9ynkNQJlo2Ec0YxwoB87m6OU22efJBu1t_or1xgev1QbrlUpKF5t8Ll5XRQWD41R0HC2ODuc4qirgm-XDLzxOpT5iyNgHfLe8Z2QK_2bWYJuzDcVXZFmlOA5R78rKjl6do1OnNtl-Pt5n6On22--bH-Th8fvPiiWagyikZ1QPpumM44ppYfqG9Qacs43WQlDG2rq9Ec50LRt4wy1vwWnuBm6HQQxicYYuD9xtinXRXOQ6TinUSElbBnzR8ZZWFz24dIo5J-vkNvlRpZ2kIPddy0PXsqbJfddyT744kqdhtOb1x_9yq4EdDLlK4Y9Nb6Lfpf4FnuCLNA</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Chen, Chih-Cheng</creator><creator>Gau, Jyh-Pyng</creator><creator>Chou, Hui-Ju</creator><creator>You, Jie-Yu</creator><creator>Huang, Cih-En</creator><creator>Chen, Yi-Yang</creator><creator>Lung, Jrhau</creator><creator>Chou, Yi-Sheng</creator><creator>Leu, Yu-Wei</creator><creator>Lu, Chang-Hsien</creator><creator>Lee, Kuan-Der</creator><creator>Tsai, Ying-Huang</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20141201</creationdate><title>Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia</title><author>Chen, Chih-Cheng ; Gau, Jyh-Pyng ; Chou, Hui-Ju ; You, Jie-Yu ; Huang, Cih-En ; Chen, Yi-Yang ; Lung, Jrhau ; Chou, Yi-Sheng ; Leu, Yu-Wei ; Lu, Chang-Hsien ; Lee, Kuan-Der ; Tsai, Ying-Huang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-921cbd47df5a2c8d9429d0ffe4cc881226014d8fd762b545e560fc5fb5ebb8b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Age Distribution</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amino Acid Sequence</topic><topic>Calreticulin - genetics</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Janus Kinase 2 - genetics</topic><topic>Kaplan-Meier Estimate</topic><topic>Leukocyte Count</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Phenotype</topic><topic>Platelet Count</topic><topic>Proportional Hazards Models</topic><topic>Receptors, Thrombopoietin - genetics</topic><topic>Sequence Alignment</topic><topic>Sequence Deletion</topic><topic>Sequence Homology, Amino Acid</topic><topic>Splenomegaly - etiology</topic><topic>Taiwan - epidemiology</topic><topic>Thrombocythemia, Essential - complications</topic><topic>Thrombocythemia, Essential - ethnology</topic><topic>Thrombocythemia, Essential - genetics</topic><topic>Thrombocythemia, Essential - mortality</topic><topic>Thrombophilia - etiology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Chih-Cheng</creatorcontrib><creatorcontrib>Gau, Jyh-Pyng</creatorcontrib><creatorcontrib>Chou, Hui-Ju</creatorcontrib><creatorcontrib>You, Jie-Yu</creatorcontrib><creatorcontrib>Huang, Cih-En</creatorcontrib><creatorcontrib>Chen, Yi-Yang</creatorcontrib><creatorcontrib>Lung, Jrhau</creatorcontrib><creatorcontrib>Chou, Yi-Sheng</creatorcontrib><creatorcontrib>Leu, Yu-Wei</creatorcontrib><creatorcontrib>Lu, Chang-Hsien</creatorcontrib><creatorcontrib>Lee, Kuan-Der</creatorcontrib><creatorcontrib>Tsai, Ying-Huang</creatorcontrib><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>Nursing & Allied Health Database</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>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</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Annals of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Chih-Cheng</au><au>Gau, Jyh-Pyng</au><au>Chou, Hui-Ju</au><au>You, Jie-Yu</au><au>Huang, Cih-En</au><au>Chen, Yi-Yang</au><au>Lung, Jrhau</au><au>Chou, Yi-Sheng</au><au>Leu, Yu-Wei</au><au>Lu, Chang-Hsien</au><au>Lee, Kuan-Der</au><au>Tsai, Ying-Huang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia</atitle><jtitle>Annals of hematology</jtitle><stitle>Ann Hematol</stitle><addtitle>Ann Hematol</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>93</volume><issue>12</issue><spage>2029</spage><epage>2036</epage><pages>2029-2036</pages><issn>0939-5555</issn><eissn>1432-0584</eissn><abstract>Calreticulin (
CALR
) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of
JAK2
and
MPL
mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients,
CALR
mutations were detected in 33 (22.5 %),
JAK2
V617F in 94 (63.9 %), and
MPL
mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (
CALR
,
JAK2
V617F, and
MPL
; triple negative). Interestingly, one patient with the type 2
CALR
mutation also harbored a low allele burden (0.025 %) of
JAK2
V617F mutation. Furthermore, we found a novel
CALR
mutation, with the resultant protein sharing an identical amino acid sequence to the type 6
CALR
mutant. Compared to those with
JAK2
mutation,
CALR-
mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis.
CARL
mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in
JAK2
-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of
CALR
mutations, and a lower platelet count (<1,000 × 10
9
/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that
CALR
mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>25015052</pmid><doi>10.1007/s00277-014-2151-8</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0939-5555 |
| ispartof | Annals of hematology, 2014-12, Vol.93 (12), p.2029-2036 |
| issn | 0939-5555 1432-0584 |
| language | eng |
| recordid | cdi_proquest_journals_1620537561 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Adult Age Distribution Aged Aged, 80 and over Amino Acid Sequence Calreticulin - genetics Female Hematology Humans Janus Kinase 2 - genetics Kaplan-Meier Estimate Leukocyte Count Male Medicine Medicine & Public Health Middle Aged Molecular Sequence Data Mutation Oncology Original Article Phenotype Platelet Count Proportional Hazards Models Receptors, Thrombopoietin - genetics Sequence Alignment Sequence Deletion Sequence Homology, Amino Acid Splenomegaly - etiology Taiwan - epidemiology Thrombocythemia, Essential - complications Thrombocythemia, Essential - ethnology Thrombocythemia, Essential - genetics Thrombocythemia, Essential - mortality Thrombophilia - etiology Young Adult |
| title | Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia |
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