Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms
The t(4;14) translocation in multiple myeloma (MM) simultaneously dysregulates two apparent oncogenes: fibroblast growth factor receptor 3 ( FGFR3 ) controlled by the 3′ immunoglobulin heavy chain enhancer on der(14) and MMSET controlled by the intronic Eμ enhancer on der(4). Although all MM tumors...
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| Veröffentlicht in: | Leukemia 2010-06, Vol.24 (6), p.1171-1178 |
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| creator | Zingone, A Cultraro, C M Shin, D-M Bean, C M Morse, H C Janz, S Kuehl, W M |
| description | The t(4;14) translocation in multiple myeloma (MM) simultaneously dysregulates two apparent oncogenes: fibroblast growth factor receptor 3 (
FGFR3
) controlled by the 3′ immunoglobulin heavy chain enhancer on der(14) and
MMSET
controlled by the intronic Eμ enhancer on der(4). Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated
MMSET
, about 25% do not express
FGFR3
. Therefore, the function of dysregulated wild-type (WT)
FGFR3
in the pathogenesis of MM remains unclear. We developed a murine transgenic (TG) model in which WT
FGFR3
is overexpressed in B lymphoid cells. Although high levels of
FGFR3
resulted in lymphoid hyperplasia in about one-third of older mice, no increase in tumorigenesis was observed. However, double TG
FGFR3
/
Myc
mice develop mature B lymphoma tumors that occur with a higher penetrance and shorter latency than in single TG
Myc
mice (
P
=0.006). We conclude that expression of high levels of WT
FGFR3
can be oncogenic and cooperate with
MYC
to generate B lymphoid tumors. This suggests that dysregulated
FGFR3
expression is likely to be essential at least for the early stages of pathogenesis of MM tumors that have a t(4;14) translocation. |
| doi_str_mv | 10.1038/leu.2010.50 |
| format | Article |
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FGFR3
) controlled by the 3′ immunoglobulin heavy chain enhancer on der(14) and
MMSET
controlled by the intronic Eμ enhancer on der(4). Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated
MMSET
, about 25% do not express
FGFR3
. Therefore, the function of dysregulated wild-type (WT)
FGFR3
in the pathogenesis of MM remains unclear. We developed a murine transgenic (TG) model in which WT
FGFR3
is overexpressed in B lymphoid cells. Although high levels of
FGFR3
resulted in lymphoid hyperplasia in about one-third of older mice, no increase in tumorigenesis was observed. However, double TG
FGFR3
/
Myc
mice develop mature B lymphoma tumors that occur with a higher penetrance and shorter latency than in single TG
Myc
mice (
P
=0.006). We conclude that expression of high levels of WT
FGFR3
can be oncogenic and cooperate with
MYC
to generate B lymphoid tumors. This suggests that dysregulated
FGFR3
expression is likely to be essential at least for the early stages of pathogenesis of MM tumors that have a t(4;14) translocation.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2010.50</identifier><identifier>PMID: 20393505</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/395 ; 692/420/2489/1381/1853 ; 692/699/67/1990/291/1621/1915 ; 692/699/67/1990/804 ; Animals ; B-cell lymphoma ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Blotting, Southern ; Blotting, Western ; Cancer Research ; Cell lineage ; Cloning ; Critical Care Medicine ; Development and progression ; Ectopic expression ; Female ; Fibroblast growth factor receptor 3 ; Fibroblast growth factor receptors ; Fibroblast growth factors ; Gene Expression Profiling ; Genes, Immunoglobulin ; Genetic aspects ; Growth factors ; Hematologic and hematopoietic diseases ; Hematology ; Humans ; Hyperplasia ; Immunodeficiencies. Immunoglobulinopathies ; Immunoenzyme Techniques ; Immunoglobulinopathies ; Immunoglobulins ; Immunopathology ; Immunophenotyping ; Immunoprecipitation ; Intensive ; Internal Medicine ; Kinases ; Latency ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Ligands ; Lymphocytes B ; Lymphocytic leukemia ; Lymphoid cells ; Lymphoma ; Lymphoma, B-Cell - etiology ; Lymphoma, B-Cell - pathology ; Male ; Medical prognosis ; Medical research ; Medical sciences ; Medicine ; Medicine & Public Health ; Mice ; Mice, Transgenic ; Multiple myeloma ; Multiple Myeloma - etiology ; Multiple Myeloma - pathology ; Mutation ; Myc protein ; Neoplasms ; Oligonucleotide Array Sequence Analysis ; Oncology ; original-article ; Pathogenesis ; Physiological aspects ; Proto-Oncogene Proteins c-myc - physiology ; Receptor, Fibroblast Growth Factor, Type 3 - physiology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Translocation ; Translocation (Genetics) ; Tumorigenesis ; Tumors</subject><ispartof>Leukemia, 2010-06, Vol.24 (6), p.1171-1178</ispartof><rights>Macmillan Publishers Limited 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2010.</rights><rights>Copyright Nature Publishing Group Jun 2010</rights><rights>2010 Macmillan Publishers Limited All rights reserved 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c632t-426d1e8066d516e28e07e0b59d74265804da6527e462dc7f7d8f893c5d6e2fe53</citedby><cites>FETCH-LOGICAL-c632t-426d1e8066d516e28e07e0b59d74265804da6527e462dc7f7d8f893c5d6e2fe53</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.2010.50$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2010.50$$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=22902100$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20393505$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zingone, A</creatorcontrib><creatorcontrib>Cultraro, C M</creatorcontrib><creatorcontrib>Shin, D-M</creatorcontrib><creatorcontrib>Bean, C M</creatorcontrib><creatorcontrib>Morse, H C</creatorcontrib><creatorcontrib>Janz, S</creatorcontrib><creatorcontrib>Kuehl, W M</creatorcontrib><title>Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>The t(4;14) translocation in multiple myeloma (MM) simultaneously dysregulates two apparent oncogenes: fibroblast growth factor receptor 3 (
FGFR3
) controlled by the 3′ immunoglobulin heavy chain enhancer on der(14) and
MMSET
controlled by the intronic Eμ enhancer on der(4). Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated
MMSET
, about 25% do not express
FGFR3
. Therefore, the function of dysregulated wild-type (WT)
FGFR3
in the pathogenesis of MM remains unclear. We developed a murine transgenic (TG) model in which WT
FGFR3
is overexpressed in B lymphoid cells. Although high levels of
FGFR3
resulted in lymphoid hyperplasia in about one-third of older mice, no increase in tumorigenesis was observed. However, double TG
FGFR3
/
Myc
mice develop mature B lymphoma tumors that occur with a higher penetrance and shorter latency than in single TG
Myc
mice (
P
=0.006). We conclude that expression of high levels of WT
FGFR3
can be oncogenic and cooperate with
MYC
to generate B lymphoid tumors. This suggests that dysregulated
FGFR3
expression is likely to be essential at least for the early stages of pathogenesis of MM tumors that have a t(4;14) translocation.</description><subject>631/67/395</subject><subject>692/420/2489/1381/1853</subject><subject>692/699/67/1990/291/1621/1915</subject><subject>692/699/67/1990/804</subject><subject>Animals</subject><subject>B-cell lymphoma</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Blotting, Southern</subject><subject>Blotting, Western</subject><subject>Cancer Research</subject><subject>Cell lineage</subject><subject>Cloning</subject><subject>Critical Care Medicine</subject><subject>Development and progression</subject><subject>Ectopic expression</subject><subject>Female</subject><subject>Fibroblast growth factor receptor 3</subject><subject>Fibroblast growth factor receptors</subject><subject>Fibroblast growth factors</subject><subject>Gene Expression Profiling</subject><subject>Genes, Immunoglobulin</subject><subject>Genetic aspects</subject><subject>Growth factors</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Humans</subject><subject>Hyperplasia</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunoenzyme Techniques</subject><subject>Immunoglobulinopathies</subject><subject>Immunoglobulins</subject><subject>Immunopathology</subject><subject>Immunophenotyping</subject><subject>Immunoprecipitation</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>Latency</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Ligands</subject><subject>Lymphocytes B</subject><subject>Lymphocytic leukemia</subject><subject>Lymphoid cells</subject><subject>Lymphoma</subject><subject>Lymphoma, B-Cell - etiology</subject><subject>Lymphoma, B-Cell - pathology</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - etiology</subject><subject>Multiple Myeloma - pathology</subject><subject>Mutation</subject><subject>Myc protein</subject><subject>Neoplasms</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oncology</subject><subject>original-article</subject><subject>Pathogenesis</subject><subject>Physiological aspects</subject><subject>Proto-Oncogene Proteins c-myc - physiology</subject><subject>Receptor, Fibroblast Growth Factor, Type 3 - physiology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Translocation</subject><subject>Translocation (Genetics)</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkktv1DAUhSMEosPAij2KQMACMvgRP7JBKqNOQSpCQrBgZbn2zYwrJw5xUui_x2GGTgcVoSys-Hw-1_f6ZNljjBYYUfnGw7ggKP0xdCeb4VLwgjGG72YzJKUoeEXKo-xBjBcITSK_nx0RRCvKEJtl4cQMoXMmh59dDzG60Oahzn84b4vhqoN8dbr6THMTQge9HiAmadjkH78t8yHk2hjwv_dzC5fgQ9dAO0wG74qk-Ny7FvQa8hZC53Vs4sPsXq19hEe7dZ59XZ18Wb4vzj6dflgenxWGUzIUJeEWg0ScW4Y5EAlIADpnlRVJYhKVVnNGBJScWCNqYWUtK2qYTXANjM6zt1vfbjxvwJp0rV571fWu0f2VCtqpQ6V1G7UOl4piLJnAyeDlzqAP30eIg2pcnHrSqZcxKlFyzBFi7P8kpYRjkmY-z57-RV6EsW_THBTlHBG-hZ79CyK8ZIJUkoo9tdYelGvrkLowU2F1TEiFuJCcJmpxC5U-C40zoYXapf2DAy9uHNiA9sMmBj8OKRfxEHy1BU0fYuyhvh4tRmqKpUqxVFMsFZt6enLzNa7ZPzlMwPMdoKPRvu51a1zcc6kuwWgyer3lYpLaNfT74dxW9xfeofXY</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Zingone, A</creator><creator>Cultraro, C M</creator><creator>Shin, D-M</creator><creator>Bean, C M</creator><creator>Morse, H C</creator><creator>Janz, S</creator><creator>Kuehl, W M</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>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100601</creationdate><title>Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms</title><author>Zingone, A ; Cultraro, C M ; Shin, D-M ; Bean, C M ; Morse, H C ; Janz, S ; Kuehl, W M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c632t-426d1e8066d516e28e07e0b59d74265804da6527e462dc7f7d8f893c5d6e2fe53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>631/67/395</topic><topic>692/420/2489/1381/1853</topic><topic>692/699/67/1990/291/1621/1915</topic><topic>692/699/67/1990/804</topic><topic>Animals</topic><topic>B-cell lymphoma</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Blotting, Southern</topic><topic>Blotting, Western</topic><topic>Cancer Research</topic><topic>Cell lineage</topic><topic>Cloning</topic><topic>Critical Care Medicine</topic><topic>Development and progression</topic><topic>Ectopic expression</topic><topic>Female</topic><topic>Fibroblast growth factor receptor 3</topic><topic>Fibroblast growth factor receptors</topic><topic>Fibroblast growth factors</topic><topic>Gene Expression Profiling</topic><topic>Genes, Immunoglobulin</topic><topic>Genetic aspects</topic><topic>Growth factors</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Humans</topic><topic>Hyperplasia</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunoenzyme Techniques</topic><topic>Immunoglobulinopathies</topic><topic>Immunoglobulins</topic><topic>Immunopathology</topic><topic>Immunophenotyping</topic><topic>Immunoprecipitation</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Kinases</topic><topic>Latency</topic><topic>Leukemia</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Ligands</topic><topic>Lymphocytes B</topic><topic>Lymphocytic leukemia</topic><topic>Lymphoid cells</topic><topic>Lymphoma</topic><topic>Lymphoma, B-Cell - etiology</topic><topic>Lymphoma, B-Cell - pathology</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - etiology</topic><topic>Multiple Myeloma - pathology</topic><topic>Mutation</topic><topic>Myc protein</topic><topic>Neoplasms</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oncology</topic><topic>original-article</topic><topic>Pathogenesis</topic><topic>Physiological aspects</topic><topic>Proto-Oncogene Proteins c-myc - physiology</topic><topic>Receptor, Fibroblast Growth Factor, Type 3 - physiology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - 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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>Zingone, A</au><au>Cultraro, C M</au><au>Shin, D-M</au><au>Bean, C M</au><au>Morse, H C</au><au>Janz, S</au><au>Kuehl, W M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>24</volume><issue>6</issue><spage>1171</spage><epage>1178</epage><pages>1171-1178</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>The t(4;14) translocation in multiple myeloma (MM) simultaneously dysregulates two apparent oncogenes: fibroblast growth factor receptor 3 (
FGFR3
) controlled by the 3′ immunoglobulin heavy chain enhancer on der(14) and
MMSET
controlled by the intronic Eμ enhancer on der(4). Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated
MMSET
, about 25% do not express
FGFR3
. Therefore, the function of dysregulated wild-type (WT)
FGFR3
in the pathogenesis of MM remains unclear. We developed a murine transgenic (TG) model in which WT
FGFR3
is overexpressed in B lymphoid cells. Although high levels of
FGFR3
resulted in lymphoid hyperplasia in about one-third of older mice, no increase in tumorigenesis was observed. However, double TG
FGFR3
/
Myc
mice develop mature B lymphoma tumors that occur with a higher penetrance and shorter latency than in single TG
Myc
mice (
P
=0.006). We conclude that expression of high levels of WT
FGFR3
can be oncogenic and cooperate with
MYC
to generate B lymphoid tumors. This suggests that dysregulated
FGFR3
expression is likely to be essential at least for the early stages of pathogenesis of MM tumors that have a t(4;14) translocation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20393505</pmid><doi>10.1038/leu.2010.50</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2010-06, Vol.24 (6), p.1171-1178 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3118571 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 631/67/395 692/420/2489/1381/1853 692/699/67/1990/291/1621/1915 692/699/67/1990/804 Animals B-cell lymphoma Biological and medical sciences Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Blotting, Southern Blotting, Western Cancer Research Cell lineage Cloning Critical Care Medicine Development and progression Ectopic expression Female Fibroblast growth factor receptor 3 Fibroblast growth factor receptors Fibroblast growth factors Gene Expression Profiling Genes, Immunoglobulin Genetic aspects Growth factors Hematologic and hematopoietic diseases Hematology Humans Hyperplasia Immunodeficiencies. Immunoglobulinopathies Immunoenzyme Techniques Immunoglobulinopathies Immunoglobulins Immunopathology Immunophenotyping Immunoprecipitation Intensive Internal Medicine Kinases Latency Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Ligands Lymphocytes B Lymphocytic leukemia Lymphoid cells Lymphoma Lymphoma, B-Cell - etiology Lymphoma, B-Cell - pathology Male Medical prognosis Medical research Medical sciences Medicine Medicine & Public Health Mice Mice, Transgenic Multiple myeloma Multiple Myeloma - etiology Multiple Myeloma - pathology Mutation Myc protein Neoplasms Oligonucleotide Array Sequence Analysis Oncology original-article Pathogenesis Physiological aspects Proto-Oncogene Proteins c-myc - physiology Receptor, Fibroblast Growth Factor, Type 3 - physiology Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Translocation Translocation (Genetics) Tumorigenesis Tumors |
| title | Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T05%3A33%3A53IST&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=Ectopic%20expression%20of%20wild-type%20FGFR3%20cooperates%20with%20MYC%20to%20accelerate%20development%20of%20B-cell%20lineage%20neoplasms&rft.jtitle=Leukemia&rft.au=Zingone,%20A&rft.date=2010-06-01&rft.volume=24&rft.issue=6&rft.spage=1171&rft.epage=1178&rft.pages=1171-1178&rft.issn=0887-6924&rft.eissn=1476-5551&rft.coden=LEUKED&rft_id=info:doi/10.1038/leu.2010.50&rft_dat=%3Cgale_pubme%3EA229067863%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=2645729837&rft_id=info:pmid/20393505&rft_galeid=A229067863&rfr_iscdi=true |