Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice
The Jak2V617F mutation is found in most classical BCR/ABL-negative myeloproliferative neoplasms (MPNs). Usually, heterozygosity of the mutation is associated with essential thrombocythemia (ET) and homozygosity with polycythemia vera (PV). Retrovirally transduced or transgenic animal models have sho...
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| Veröffentlicht in: | Blood 2010-08, Vol.116 (5), p.783-787 |
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| creator | Marty, Caroline Lacout, Catherine Martin, Antoine Hasan, Salma Jacquot, Sylvie Birling, Marie-Christine Vainchenker, William Villeval, Jean-Luc |
| description | The Jak2V617F mutation is found in most classical BCR/ABL-negative myeloproliferative neoplasms (MPNs). Usually, heterozygosity of the mutation is associated with essential thrombocythemia (ET) and homozygosity with polycythemia vera (PV). Retrovirally transduced or transgenic animal models have shown that the mutation is sufficient for MPN development but that the level of expression is crucial for MPN phenotypes. Therefore we investigated the effect of an endogenous heterozygous expression of Jak2V617F in knock-in (KI) mice. These animals displayed constitutive JAK2 activation and autonomous erythroid progenitor cell growth. Mice suffered from marked polycythemia, granulocytosis and thrombocytosis. Spleens and marrows displayed myeloid trilineage hyperplasia. Most animals survived to develop advanced fibrosis in these organs at around 9 months of age. In conclusion, constitutive heterozygous expression of JAK2V617F in mice is not embryo-lethal but results in severe PV-like disease with secondary myelofibrosis and not in ET-like disease as expected from patient study. |
| doi_str_mv | 10.1182/blood-2009-12-257063 |
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Usually, heterozygosity of the mutation is associated with essential thrombocythemia (ET) and homozygosity with polycythemia vera (PV). Retrovirally transduced or transgenic animal models have shown that the mutation is sufficient for MPN development but that the level of expression is crucial for MPN phenotypes. Therefore we investigated the effect of an endogenous heterozygous expression of Jak2V617F in knock-in (KI) mice. These animals displayed constitutive JAK2 activation and autonomous erythroid progenitor cell growth. Mice suffered from marked polycythemia, granulocytosis and thrombocytosis. Spleens and marrows displayed myeloid trilineage hyperplasia. Most animals survived to develop advanced fibrosis in these organs at around 9 months of age. In conclusion, constitutive heterozygous expression of JAK2V617F in mice is not embryo-lethal but results in severe PV-like disease with secondary myelofibrosis and not in ET-like disease as expected from patient study.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2009-12-257063</identifier><identifier>PMID: 20472827</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Amino Acid Substitution ; Animal biology ; Animals ; Biological and medical sciences ; Bone Marrow - pathology ; Cell Lineage ; Crosses, Genetic ; Gene Knock-In Techniques ; Hematologic and hematopoietic diseases ; Heterozygote ; Humans ; Hyperplasia ; Janus Kinase 2 - genetics ; Janus Kinase 2 - physiology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Life Sciences ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation, Missense ; Myeloproliferative Disorders - enzymology ; Myeloproliferative Disorders - etiology ; Myeloproliferative Disorders - genetics ; Point Mutation ; Polycythemia Vera - enzymology ; Polycythemia Vera - genetics ; Primary Myelofibrosis - enzymology ; Primary Myelofibrosis - etiology ; Primary Myelofibrosis - genetics ; Spleen - pathology ; Thrombocythemia, Essential - enzymology ; Thrombocythemia, Essential - genetics</subject><ispartof>Blood, 2010-08, Vol.116 (5), p.783-787</ispartof><rights>2010 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3823-1d074149bcfe64a7f0c088e36e99a7494901548c5f2a6f22c14c82f51587523</citedby><cites>FETCH-LOGICAL-c3823-1d074149bcfe64a7f0c088e36e99a7494901548c5f2a6f22c14c82f51587523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23087370$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20472827$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04050143$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Marty, Caroline</creatorcontrib><creatorcontrib>Lacout, Catherine</creatorcontrib><creatorcontrib>Martin, Antoine</creatorcontrib><creatorcontrib>Hasan, Salma</creatorcontrib><creatorcontrib>Jacquot, Sylvie</creatorcontrib><creatorcontrib>Birling, Marie-Christine</creatorcontrib><creatorcontrib>Vainchenker, William</creatorcontrib><creatorcontrib>Villeval, Jean-Luc</creatorcontrib><title>Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice</title><title>Blood</title><addtitle>Blood</addtitle><description>The Jak2V617F mutation is found in most classical BCR/ABL-negative myeloproliferative neoplasms (MPNs). Usually, heterozygosity of the mutation is associated with essential thrombocythemia (ET) and homozygosity with polycythemia vera (PV). Retrovirally transduced or transgenic animal models have shown that the mutation is sufficient for MPN development but that the level of expression is crucial for MPN phenotypes. Therefore we investigated the effect of an endogenous heterozygous expression of Jak2V617F in knock-in (KI) mice. These animals displayed constitutive JAK2 activation and autonomous erythroid progenitor cell growth. Mice suffered from marked polycythemia, granulocytosis and thrombocytosis. Spleens and marrows displayed myeloid trilineage hyperplasia. Most animals survived to develop advanced fibrosis in these organs at around 9 months of age. In conclusion, constitutive heterozygous expression of JAK2V617F in mice is not embryo-lethal but results in severe PV-like disease with secondary myelofibrosis and not in ET-like disease as expected from patient study.</description><subject>Amino Acid Substitution</subject><subject>Animal biology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow - pathology</subject><subject>Cell Lineage</subject><subject>Crosses, Genetic</subject><subject>Gene Knock-In Techniques</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Hyperplasia</subject><subject>Janus Kinase 2 - genetics</subject><subject>Janus Kinase 2 - physiology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Life Sciences</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Mutation, Missense</subject><subject>Myeloproliferative Disorders - enzymology</subject><subject>Myeloproliferative Disorders - etiology</subject><subject>Myeloproliferative Disorders - genetics</subject><subject>Point Mutation</subject><subject>Polycythemia Vera - enzymology</subject><subject>Polycythemia Vera - genetics</subject><subject>Primary Myelofibrosis - enzymology</subject><subject>Primary Myelofibrosis - etiology</subject><subject>Primary Myelofibrosis - genetics</subject><subject>Spleen - pathology</subject><subject>Thrombocythemia, Essential - enzymology</subject><subject>Thrombocythemia, Essential - genetics</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAQhi1ERbeFN0AoFw4cDOOJHTsXpFVFW2CrHoo4IVleZyxMs3Fk767YtyfblHLjNKPR949mPsZeC3gvhMEP6z6ljiNAywVyVBqa-hlbCIWGAyA8ZwsAaLhstThlZ6X8AhCyRvWCnSJIjQb1gv24OVCfxpz6GCi7bdxTNVAae1c2VRy6naeuWh8qn4ayjdvdA0C_x0ylxDRUKVRfll_xeyP05cRX90Py93xqNtHTS3YSXF_o1WM9Z3eXn75dXPPV7dXni-WK-9pgzUUHWgrZrn2gRjodwIMxVDfUtk7LVrYglDReBXRNQPRCeoNBCWW0wvqcvZu3_nS9HXPcuHywyUV7vVzZ4wwkqOPrezGxcmZ9TqVkCk8BAfao1T5otUetVqCdtU6xN3Ns3K031D2F_nqcgLePgCve9SG7wcfyj6vB6FrDxH2cOZp07CNlW3ykYZIcM_mt7VL8_yV_AKzClG0</recordid><startdate>20100805</startdate><enddate>20100805</enddate><creator>Marty, Caroline</creator><creator>Lacout, Catherine</creator><creator>Martin, Antoine</creator><creator>Hasan, Salma</creator><creator>Jacquot, Sylvie</creator><creator>Birling, Marie-Christine</creator><creator>Vainchenker, William</creator><creator>Villeval, Jean-Luc</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><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>1XC</scope></search><sort><creationdate>20100805</creationdate><title>Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice</title><author>Marty, Caroline ; Lacout, Catherine ; Martin, Antoine ; Hasan, Salma ; Jacquot, Sylvie ; Birling, Marie-Christine ; Vainchenker, William ; Villeval, Jean-Luc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3823-1d074149bcfe64a7f0c088e36e99a7494901548c5f2a6f22c14c82f51587523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amino Acid Substitution</topic><topic>Animal biology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow - pathology</topic><topic>Cell Lineage</topic><topic>Crosses, Genetic</topic><topic>Gene Knock-In Techniques</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Heterozygote</topic><topic>Humans</topic><topic>Hyperplasia</topic><topic>Janus Kinase 2 - genetics</topic><topic>Janus Kinase 2 - physiology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Life Sciences</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Mutation, Missense</topic><topic>Myeloproliferative Disorders - enzymology</topic><topic>Myeloproliferative Disorders - etiology</topic><topic>Myeloproliferative Disorders - genetics</topic><topic>Point Mutation</topic><topic>Polycythemia Vera - enzymology</topic><topic>Polycythemia Vera - genetics</topic><topic>Primary Myelofibrosis - enzymology</topic><topic>Primary Myelofibrosis - etiology</topic><topic>Primary Myelofibrosis - genetics</topic><topic>Spleen - pathology</topic><topic>Thrombocythemia, Essential - enzymology</topic><topic>Thrombocythemia, Essential - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marty, Caroline</creatorcontrib><creatorcontrib>Lacout, Catherine</creatorcontrib><creatorcontrib>Martin, Antoine</creatorcontrib><creatorcontrib>Hasan, Salma</creatorcontrib><creatorcontrib>Jacquot, Sylvie</creatorcontrib><creatorcontrib>Birling, Marie-Christine</creatorcontrib><creatorcontrib>Vainchenker, William</creatorcontrib><creatorcontrib>Villeval, Jean-Luc</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Hyper Article en Ligne (HAL)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marty, Caroline</au><au>Lacout, Catherine</au><au>Martin, Antoine</au><au>Hasan, Salma</au><au>Jacquot, Sylvie</au><au>Birling, Marie-Christine</au><au>Vainchenker, William</au><au>Villeval, Jean-Luc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2010-08-05</date><risdate>2010</risdate><volume>116</volume><issue>5</issue><spage>783</spage><epage>787</epage><pages>783-787</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>The Jak2V617F mutation is found in most classical BCR/ABL-negative myeloproliferative neoplasms (MPNs). Usually, heterozygosity of the mutation is associated with essential thrombocythemia (ET) and homozygosity with polycythemia vera (PV). Retrovirally transduced or transgenic animal models have shown that the mutation is sufficient for MPN development but that the level of expression is crucial for MPN phenotypes. Therefore we investigated the effect of an endogenous heterozygous expression of Jak2V617F in knock-in (KI) mice. These animals displayed constitutive JAK2 activation and autonomous erythroid progenitor cell growth. Mice suffered from marked polycythemia, granulocytosis and thrombocytosis. Spleens and marrows displayed myeloid trilineage hyperplasia. Most animals survived to develop advanced fibrosis in these organs at around 9 months of age. In conclusion, constitutive heterozygous expression of JAK2V617F in mice is not embryo-lethal but results in severe PV-like disease with secondary myelofibrosis and not in ET-like disease as expected from patient study.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>20472827</pmid><doi>10.1182/blood-2009-12-257063</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Substitution Animal biology Animals Biological and medical sciences Bone Marrow - pathology Cell Lineage Crosses, Genetic Gene Knock-In Techniques Hematologic and hematopoietic diseases Heterozygote Humans Hyperplasia Janus Kinase 2 - genetics Janus Kinase 2 - physiology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Life Sciences Medical sciences Mice Mice, Inbred C57BL Mice, Transgenic Mutation, Missense Myeloproliferative Disorders - enzymology Myeloproliferative Disorders - etiology Myeloproliferative Disorders - genetics Point Mutation Polycythemia Vera - enzymology Polycythemia Vera - genetics Primary Myelofibrosis - enzymology Primary Myelofibrosis - etiology Primary Myelofibrosis - genetics Spleen - pathology Thrombocythemia, Essential - enzymology Thrombocythemia, Essential - genetics |
| title | Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice |
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