Functional characterization of two rare BCR-FGFR1 + leukemias
8p11 myeloproliferative syndrome (EMS) represents a unique World Health Organization (WHO)-classified hematologic malignancy defined by translocations of the FGFR1 receptor. The syndrome is a myeloproliferative neoplasm characterized by eosinophilia and lymphadenopathy, with risk of progression to e...
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| Veröffentlicht in: | Cold Spring Harbor molecular case studies 2020-04, Vol.6 (2), p.a004838 |
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| creator | Barnes, Evan J Leonard, Jessica Medeiros, Bruno C Druker, Brian J Tognon, Cristina E |
| description | 8p11 myeloproliferative syndrome (EMS) represents a unique World Health Organization (WHO)-classified hematologic malignancy defined by translocations of the FGFR1 receptor. The syndrome is a myeloproliferative neoplasm characterized by eosinophilia and lymphadenopathy, with risk of progression to either acute myeloid leukemia (AML) or T- or B-lymphoblastic lymphoma/leukemia. Within the EMS subtype, translocations between
(
) and
(
) have been shown to produce a dominant fusion protein that is notoriously resistant to tyrosine kinase inhibitors (TKIs). Here, we report two cases of
EMS identified via RNA sequencing (RNA-seq) and confirmed by fluorescence in situ hybridization (FISH). Sanger sequencing revealed that both cases harbored the exact same breakpoint. In the first case, the patient presented with AML-like disease, and in the second, the patient progressed to B-cell acute lymphoblastic leukemia (B-ALL). Additionally, we observed that that primary leukemia cells from Case 1 demonstrated sensitivity to the tyrosine kinase inhibitors ponatinib and dovitinib that can target FGFR1 kinase activity, whereas primary cells from Case 2 were resistant to both drugs. Taken together, these results suggest that some but not all BCR-FGFR1 fusion positive leukemias may respond to TKIs that target FGFR1 kinase activity. |
| doi_str_mv | 10.1101/mcs.a004838 |
| format | Article |
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(
) and
(
) have been shown to produce a dominant fusion protein that is notoriously resistant to tyrosine kinase inhibitors (TKIs). Here, we report two cases of
EMS identified via RNA sequencing (RNA-seq) and confirmed by fluorescence in situ hybridization (FISH). Sanger sequencing revealed that both cases harbored the exact same breakpoint. In the first case, the patient presented with AML-like disease, and in the second, the patient progressed to B-cell acute lymphoblastic leukemia (B-ALL). Additionally, we observed that that primary leukemia cells from Case 1 demonstrated sensitivity to the tyrosine kinase inhibitors ponatinib and dovitinib that can target FGFR1 kinase activity, whereas primary cells from Case 2 were resistant to both drugs. Taken together, these results suggest that some but not all BCR-FGFR1 fusion positive leukemias may respond to TKIs that target FGFR1 kinase activity.</description><identifier>ISSN: 2373-2865</identifier><identifier>EISSN: 2373-2873</identifier><identifier>DOI: 10.1101/mcs.a004838</identifier><identifier>PMID: 31980503</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Acute lymphoblastic leukemia ; Acute myeloid leukemia ; BCR-ABL protein ; Eosinophilia ; Fibroblast growth factor receptor 1 ; Fluorescence ; Fluorescence in situ hybridization ; Fusion protein ; Gene sequencing ; Growth factors ; Inhibitors ; Kinases ; Leukemia ; Lymphadenopathy ; Lymphatic leukemia ; Lymphocytes B ; Lymphoma ; Malignancy ; Myeloid leukemia ; Neoplasia ; Protein-tyrosine kinase ; Receptors ; Research Report ; Ribonucleic acid ; RNA ; Translocation ; Tyrosine</subject><ispartof>Cold Spring Harbor molecular case studies, 2020-04, Vol.6 (2), p.a004838</ispartof><rights>2020 Barnes et al.; Published by Cold Spring Harbor Laboratory Press.</rights><rights>Copyright Cold Spring Harbor Laboratory Press Apr 2020</rights><rights>2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-8d7b0defd615f16b890eeda2620007368cd7bf179da20eb3b128ec80141d517a3</citedby><cites>FETCH-LOGICAL-c409t-8d7b0defd615f16b890eeda2620007368cd7bf179da20eb3b128ec80141d517a3</cites><orcidid>0000-0002-4872-3078 ; 0000-0001-6972-8137</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133745/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133745/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31980503$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barnes, Evan J</creatorcontrib><creatorcontrib>Leonard, Jessica</creatorcontrib><creatorcontrib>Medeiros, Bruno C</creatorcontrib><creatorcontrib>Druker, Brian J</creatorcontrib><creatorcontrib>Tognon, Cristina E</creatorcontrib><title>Functional characterization of two rare BCR-FGFR1 + leukemias</title><title>Cold Spring Harbor molecular case studies</title><addtitle>Cold Spring Harb Mol Case Stud</addtitle><description>8p11 myeloproliferative syndrome (EMS) represents a unique World Health Organization (WHO)-classified hematologic malignancy defined by translocations of the FGFR1 receptor. The syndrome is a myeloproliferative neoplasm characterized by eosinophilia and lymphadenopathy, with risk of progression to either acute myeloid leukemia (AML) or T- or B-lymphoblastic lymphoma/leukemia. Within the EMS subtype, translocations between
(
) and
(
) have been shown to produce a dominant fusion protein that is notoriously resistant to tyrosine kinase inhibitors (TKIs). Here, we report two cases of
EMS identified via RNA sequencing (RNA-seq) and confirmed by fluorescence in situ hybridization (FISH). Sanger sequencing revealed that both cases harbored the exact same breakpoint. In the first case, the patient presented with AML-like disease, and in the second, the patient progressed to B-cell acute lymphoblastic leukemia (B-ALL). Additionally, we observed that that primary leukemia cells from Case 1 demonstrated sensitivity to the tyrosine kinase inhibitors ponatinib and dovitinib that can target FGFR1 kinase activity, whereas primary cells from Case 2 were resistant to both drugs. Taken together, these results suggest that some but not all BCR-FGFR1 fusion positive leukemias may respond to TKIs that target FGFR1 kinase activity.</description><subject>Acute lymphoblastic leukemia</subject><subject>Acute myeloid leukemia</subject><subject>BCR-ABL protein</subject><subject>Eosinophilia</subject><subject>Fibroblast growth factor receptor 1</subject><subject>Fluorescence</subject><subject>Fluorescence in situ hybridization</subject><subject>Fusion protein</subject><subject>Gene sequencing</subject><subject>Growth factors</subject><subject>Inhibitors</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Lymphadenopathy</subject><subject>Lymphatic leukemia</subject><subject>Lymphocytes B</subject><subject>Lymphoma</subject><subject>Malignancy</subject><subject>Myeloid leukemia</subject><subject>Neoplasia</subject><subject>Protein-tyrosine kinase</subject><subject>Receptors</subject><subject>Research Report</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Translocation</subject><subject>Tyrosine</subject><issn>2373-2865</issn><issn>2373-2873</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpdkdFLwzAQxoMobsw9-S4FX4TReWmaJn1Q0OGmMBCGPoc0TV1n28ykVfSvN2NzqA_HHXc_Pj7uQ-gUwxhjwJe1cmMJEHPCD1A_IoyEEWfkcD8ntIeGzq0AACdJSll0jHoEpxwokD66mnaNakvTyCpQS2mlarUtv-RmFZgiaD9MYKXVwe1kEU5n0wUORkGlu1ddl9KdoKNCVk4Pd32Anqd3T5P7cP44e5jczEMVQ9qGPGcZ5LrIE0wLnGQ8Ba1zGSWRd8VIwpUHCsxSvwOdkQxHXCsOOMY5xUySAbre6q67rNa50k1rZSXWtqyl_RRGluLvpSmX4sW8C4YJYTH1Ahc7AWveOu1aUZdO6aqSjTadExGJKQUGMfHo-T90ZTrr_7Oh0ihmzJenRltKWeOc1cXeDAaxSUb4ZMQuGU-f_fa_Z39yIN8UB4gI</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Barnes, Evan J</creator><creator>Leonard, Jessica</creator><creator>Medeiros, Bruno C</creator><creator>Druker, Brian J</creator><creator>Tognon, Cristina E</creator><general>Cold Spring Harbor Laboratory Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4872-3078</orcidid><orcidid>https://orcid.org/0000-0001-6972-8137</orcidid></search><sort><creationdate>20200401</creationdate><title>Functional characterization of two rare BCR-FGFR1 + leukemias</title><author>Barnes, Evan J ; Leonard, Jessica ; Medeiros, Bruno C ; Druker, Brian J ; Tognon, Cristina E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-8d7b0defd615f16b890eeda2620007368cd7bf179da20eb3b128ec80141d517a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Acute myeloid leukemia</topic><topic>BCR-ABL protein</topic><topic>Eosinophilia</topic><topic>Fibroblast growth factor receptor 1</topic><topic>Fluorescence</topic><topic>Fluorescence in situ hybridization</topic><topic>Fusion protein</topic><topic>Gene sequencing</topic><topic>Growth factors</topic><topic>Inhibitors</topic><topic>Kinases</topic><topic>Leukemia</topic><topic>Lymphadenopathy</topic><topic>Lymphatic leukemia</topic><topic>Lymphocytes B</topic><topic>Lymphoma</topic><topic>Malignancy</topic><topic>Myeloid leukemia</topic><topic>Neoplasia</topic><topic>Protein-tyrosine kinase</topic><topic>Receptors</topic><topic>Research Report</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Translocation</topic><topic>Tyrosine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barnes, Evan J</creatorcontrib><creatorcontrib>Leonard, Jessica</creatorcontrib><creatorcontrib>Medeiros, Bruno C</creatorcontrib><creatorcontrib>Druker, Brian J</creatorcontrib><creatorcontrib>Tognon, Cristina E</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cold Spring Harbor molecular case studies</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barnes, Evan J</au><au>Leonard, Jessica</au><au>Medeiros, Bruno C</au><au>Druker, Brian J</au><au>Tognon, Cristina E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional characterization of two rare BCR-FGFR1 + leukemias</atitle><jtitle>Cold Spring Harbor molecular case studies</jtitle><addtitle>Cold Spring Harb Mol Case Stud</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>6</volume><issue>2</issue><spage>a004838</spage><pages>a004838-</pages><issn>2373-2865</issn><eissn>2373-2873</eissn><abstract>8p11 myeloproliferative syndrome (EMS) represents a unique World Health Organization (WHO)-classified hematologic malignancy defined by translocations of the FGFR1 receptor. The syndrome is a myeloproliferative neoplasm characterized by eosinophilia and lymphadenopathy, with risk of progression to either acute myeloid leukemia (AML) or T- or B-lymphoblastic lymphoma/leukemia. Within the EMS subtype, translocations between
(
) and
(
) have been shown to produce a dominant fusion protein that is notoriously resistant to tyrosine kinase inhibitors (TKIs). Here, we report two cases of
EMS identified via RNA sequencing (RNA-seq) and confirmed by fluorescence in situ hybridization (FISH). Sanger sequencing revealed that both cases harbored the exact same breakpoint. In the first case, the patient presented with AML-like disease, and in the second, the patient progressed to B-cell acute lymphoblastic leukemia (B-ALL). Additionally, we observed that that primary leukemia cells from Case 1 demonstrated sensitivity to the tyrosine kinase inhibitors ponatinib and dovitinib that can target FGFR1 kinase activity, whereas primary cells from Case 2 were resistant to both drugs. Taken together, these results suggest that some but not all BCR-FGFR1 fusion positive leukemias may respond to TKIs that target FGFR1 kinase activity.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>31980503</pmid><doi>10.1101/mcs.a004838</doi><orcidid>https://orcid.org/0000-0002-4872-3078</orcidid><orcidid>https://orcid.org/0000-0001-6972-8137</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Acute lymphoblastic leukemia Acute myeloid leukemia BCR-ABL protein Eosinophilia Fibroblast growth factor receptor 1 Fluorescence Fluorescence in situ hybridization Fusion protein Gene sequencing Growth factors Inhibitors Kinases Leukemia Lymphadenopathy Lymphatic leukemia Lymphocytes B Lymphoma Malignancy Myeloid leukemia Neoplasia Protein-tyrosine kinase Receptors Research Report Ribonucleic acid RNA Translocation Tyrosine |
| title | Functional characterization of two rare BCR-FGFR1 + leukemias |
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