Reduced CXCR4-expression on CD34-positive blood cells predicts outcomes of persons with primary myelofibrosis
The expression of the CXCR4 chemokine receptor on CD34-positive blood cells is reduced in persons with primary myelofibrosis (PMF). We analyzed the relevance of cytofluorimetric assessment of the percentage of CD34-positive blood cells that had a positive CXCR4 surface expression (CD34/CXCR4-se) in...
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| Veröffentlicht in: | Leukemia 2021-02, Vol.35 (2), p.468-475 |
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| creator | Barosi, Giovanni Rosti, Vittorio Catarsi, Paolo Villani, Laura Abbà, Carlotta Carolei, Adriana Magrini, Umberto Gale, Robert Peter Massa, Margherita Campanelli, Rita |
| description | The expression of the CXCR4 chemokine receptor on CD34-positive blood cells is reduced in persons with primary myelofibrosis (PMF). We analyzed the relevance of cytofluorimetric assessment of the percentage of CD34-positive blood cells that had a positive CXCR4 surface expression (CD34/CXCR4-se) in a large cohort of subjects with myeloproliferative neoplasms. Mean CD34/CXCR4-se was lower in subjects with PMF compared with those with essential thrombocythemia (ET) or polycythemia vera (PV). A cutoff value of 39% was associated with a diagnosis of pre-fibrotic PMF vs. ET with a positive predictive value of 97%. In PMF male sex, older age, and
MPL
mutation were independent correlates of reduced CD34/CXCR4-se and associated with a briefer interval to development of severe anemia, large splenomegaly, thrombocytopenia, leukopenia, elevated CD34-positive blood cells, blast transformation and death. We constructed a prognostic model including age >65 years, hemoglobin 50 × 10
6
/L, and CD34/CXCR4-se |
| doi_str_mv | 10.1038/s41375-020-0926-6 |
| format | Article |
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MPL
mutation were independent correlates of reduced CD34/CXCR4-se and associated with a briefer interval to development of severe anemia, large splenomegaly, thrombocytopenia, leukopenia, elevated CD34-positive blood cells, blast transformation and death. We constructed a prognostic model including age >65 years, hemoglobin < 100 g/L, CD34-positive blood cells > 50 × 10
6
/L, and CD34/CXCR4-se <39% at diagnosis. The model identified three risk cohorts with greater accuracy compared with the International Prognostic Scoring System. In conclusion, CD34/CXCR4-se is a highly sensitive marker of disease activity and a new potential diagnostic and prognostic biomarker in PMF.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-020-0926-6</identifier><identifier>PMID: 32536689</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/21 ; 13/31 ; 45/77 ; 631/67 ; 692/420 ; Aged ; Anemia ; Antigens, CD34 - metabolism ; Biomarkers ; Biomarkers - metabolism ; Blood ; Blood cancer ; Blood cells ; Blood Cells - metabolism ; Cancer Research ; Care and treatment ; Case-Control Studies ; CD34 antigen ; Cell death ; Chemokines ; Cohort Studies ; Critical Care Medicine ; CXCR4 protein ; Development and progression ; Diagnosis ; Diagnostic systems ; Female ; Fibrosis ; Gene expression ; Genetic aspects ; Health aspects ; Hematology ; Hemoglobin ; Humans ; Intensive ; Internal Medicine ; Leukopenia ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Mutation ; Myelofibrosis ; Neoplasms ; Oncology ; Polycythemia ; Polycythemia vera ; Primary Myelofibrosis - diagnosis ; Primary Myelofibrosis - metabolism ; Prognosis ; Receptors, CXCR4 - metabolism ; Signal Transduction ; Splenomegaly ; Survival Rate ; Thrombocytopenia</subject><ispartof>Leukemia, 2021-02, Vol.35 (2), p.468-475</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-3a97ab8210656cb36ebbd8d74aee4ff581e341dc0de8eb471439cd0e6d5659353</citedby><cites>FETCH-LOGICAL-c470t-3a97ab8210656cb36ebbd8d74aee4ff581e341dc0de8eb471439cd0e6d5659353</cites><orcidid>0000-0002-8357-7192 ; 0000-0002-1862-8168</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41375-020-0926-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41375-020-0926-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32536689$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barosi, Giovanni</creatorcontrib><creatorcontrib>Rosti, Vittorio</creatorcontrib><creatorcontrib>Catarsi, Paolo</creatorcontrib><creatorcontrib>Villani, Laura</creatorcontrib><creatorcontrib>Abbà, Carlotta</creatorcontrib><creatorcontrib>Carolei, Adriana</creatorcontrib><creatorcontrib>Magrini, Umberto</creatorcontrib><creatorcontrib>Gale, Robert Peter</creatorcontrib><creatorcontrib>Massa, Margherita</creatorcontrib><creatorcontrib>Campanelli, Rita</creatorcontrib><title>Reduced CXCR4-expression on CD34-positive blood cells predicts outcomes of persons with primary myelofibrosis</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>The expression of the CXCR4 chemokine receptor on CD34-positive blood cells is reduced in persons with primary myelofibrosis (PMF). We analyzed the relevance of cytofluorimetric assessment of the percentage of CD34-positive blood cells that had a positive CXCR4 surface expression (CD34/CXCR4-se) in a large cohort of subjects with myeloproliferative neoplasms. Mean CD34/CXCR4-se was lower in subjects with PMF compared with those with essential thrombocythemia (ET) or polycythemia vera (PV). A cutoff value of 39% was associated with a diagnosis of pre-fibrotic PMF vs. ET with a positive predictive value of 97%. In PMF male sex, older age, and
MPL
mutation were independent correlates of reduced CD34/CXCR4-se and associated with a briefer interval to development of severe anemia, large splenomegaly, thrombocytopenia, leukopenia, elevated CD34-positive blood cells, blast transformation and death. We constructed a prognostic model including age >65 years, hemoglobin < 100 g/L, CD34-positive blood cells > 50 × 10
6
/L, and CD34/CXCR4-se <39% at diagnosis. The model identified three risk cohorts with greater accuracy compared with the International Prognostic Scoring System. In conclusion, CD34/CXCR4-se is a highly sensitive marker of disease activity and a new potential diagnostic and prognostic biomarker in PMF.</description><subject>13/21</subject><subject>13/31</subject><subject>45/77</subject><subject>631/67</subject><subject>692/420</subject><subject>Aged</subject><subject>Anemia</subject><subject>Antigens, CD34 - metabolism</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Blood</subject><subject>Blood cancer</subject><subject>Blood cells</subject><subject>Blood Cells - metabolism</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Case-Control Studies</subject><subject>CD34 antigen</subject><subject>Cell death</subject><subject>Chemokines</subject><subject>Cohort Studies</subject><subject>Critical Care Medicine</subject><subject>CXCR4 protein</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Hematology</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Leukopenia</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Myelofibrosis</subject><subject>Neoplasms</subject><subject>Oncology</subject><subject>Polycythemia</subject><subject>Polycythemia vera</subject><subject>Primary Myelofibrosis - diagnosis</subject><subject>Primary Myelofibrosis - metabolism</subject><subject>Prognosis</subject><subject>Receptors, CXCR4 - metabolism</subject><subject>Signal Transduction</subject><subject>Splenomegaly</subject><subject>Survival Rate</subject><subject>Thrombocytopenia</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1km1r1TAUx4M43HX6AXwjBUF8k5nnNi9HfRoMBkPBd6FNTncz2uba06r79qbcq9tESSAh-Z0_5-FPyAvOTjmT1VtUXJaaMsEos8JQ84hsuCoN1Vrzx2TDqqqkxgp1TJ4i3jC2fpon5FgKLY2p7IYMVxAWD6Gov9ZXisLP3QSIMY1F3vU7qeguYZzjdyjaPqVQeOh7LDIVop-xSMvs0wD50hU7mDCNWPyI8zYTcWim22K4hT51sZ2yDD4jR13TIzw_nCfky4f3n-tP9OLy43l9dkG9KtlMZWPLpq0EZ0Yb30oDbRuqUKoGQHWdrjhIxYNnASpoVcmVtD4wMEEbbaWWJ-TNXnc3pW8L4OyGiGvmzQhpQSdy46y1WpmMvvoLvUnLNObsMlUZYaXV-o66bnpwcezSPDV-FXVnRuuSGyVEpk7_QeUVYIg-jdDF_P4g4PW9gC00_bzF1C9zHgA-BPke9LmPOEHnDv11nLnVC27vBZe94FYvuLWyl4fKlnaA8Cfi9_AzIPYA5q_xGqa70v-v-gvkSb0K</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Barosi, Giovanni</creator><creator>Rosti, Vittorio</creator><creator>Catarsi, Paolo</creator><creator>Villani, Laura</creator><creator>Abbà, Carlotta</creator><creator>Carolei, Adriana</creator><creator>Magrini, Umberto</creator><creator>Gale, Robert Peter</creator><creator>Massa, Margherita</creator><creator>Campanelli, Rita</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>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><orcidid>https://orcid.org/0000-0002-8357-7192</orcidid><orcidid>https://orcid.org/0000-0002-1862-8168</orcidid></search><sort><creationdate>20210201</creationdate><title>Reduced CXCR4-expression on CD34-positive blood cells predicts outcomes of persons with primary myelofibrosis</title><author>Barosi, Giovanni ; Rosti, Vittorio ; Catarsi, Paolo ; Villani, Laura ; Abbà, Carlotta ; Carolei, Adriana ; Magrini, Umberto ; Gale, Robert Peter ; Massa, Margherita ; Campanelli, Rita</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-3a97ab8210656cb36ebbd8d74aee4ff581e341dc0de8eb471439cd0e6d5659353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>13/21</topic><topic>13/31</topic><topic>45/77</topic><topic>631/67</topic><topic>692/420</topic><topic>Aged</topic><topic>Anemia</topic><topic>Antigens, CD34 - metabolism</topic><topic>Biomarkers</topic><topic>Biomarkers - metabolism</topic><topic>Blood</topic><topic>Blood cancer</topic><topic>Blood cells</topic><topic>Blood Cells - metabolism</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Case-Control Studies</topic><topic>CD34 antigen</topic><topic>Cell death</topic><topic>Chemokines</topic><topic>Cohort Studies</topic><topic>Critical Care Medicine</topic><topic>CXCR4 protein</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Diagnostic systems</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Hematology</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Leukopenia</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Myelofibrosis</topic><topic>Neoplasms</topic><topic>Oncology</topic><topic>Polycythemia</topic><topic>Polycythemia vera</topic><topic>Primary Myelofibrosis - diagnosis</topic><topic>Primary Myelofibrosis - metabolism</topic><topic>Prognosis</topic><topic>Receptors, CXCR4 - metabolism</topic><topic>Signal Transduction</topic><topic>Splenomegaly</topic><topic>Survival Rate</topic><topic>Thrombocytopenia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barosi, Giovanni</creatorcontrib><creatorcontrib>Rosti, Vittorio</creatorcontrib><creatorcontrib>Catarsi, Paolo</creatorcontrib><creatorcontrib>Villani, Laura</creatorcontrib><creatorcontrib>Abbà, Carlotta</creatorcontrib><creatorcontrib>Carolei, Adriana</creatorcontrib><creatorcontrib>Magrini, Umberto</creatorcontrib><creatorcontrib>Gale, Robert Peter</creatorcontrib><creatorcontrib>Massa, Margherita</creatorcontrib><creatorcontrib>Campanelli, Rita</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Proquest Nursing & Allied Health Source</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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barosi, Giovanni</au><au>Rosti, Vittorio</au><au>Catarsi, Paolo</au><au>Villani, Laura</au><au>Abbà, Carlotta</au><au>Carolei, Adriana</au><au>Magrini, Umberto</au><au>Gale, Robert Peter</au><au>Massa, Margherita</au><au>Campanelli, Rita</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced CXCR4-expression on CD34-positive blood cells predicts outcomes of persons with primary myelofibrosis</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>35</volume><issue>2</issue><spage>468</spage><epage>475</epage><pages>468-475</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>The expression of the CXCR4 chemokine receptor on CD34-positive blood cells is reduced in persons with primary myelofibrosis (PMF). We analyzed the relevance of cytofluorimetric assessment of the percentage of CD34-positive blood cells that had a positive CXCR4 surface expression (CD34/CXCR4-se) in a large cohort of subjects with myeloproliferative neoplasms. Mean CD34/CXCR4-se was lower in subjects with PMF compared with those with essential thrombocythemia (ET) or polycythemia vera (PV). A cutoff value of 39% was associated with a diagnosis of pre-fibrotic PMF vs. ET with a positive predictive value of 97%. In PMF male sex, older age, and
MPL
mutation were independent correlates of reduced CD34/CXCR4-se and associated with a briefer interval to development of severe anemia, large splenomegaly, thrombocytopenia, leukopenia, elevated CD34-positive blood cells, blast transformation and death. We constructed a prognostic model including age >65 years, hemoglobin < 100 g/L, CD34-positive blood cells > 50 × 10
6
/L, and CD34/CXCR4-se <39% at diagnosis. The model identified three risk cohorts with greater accuracy compared with the International Prognostic Scoring System. In conclusion, CD34/CXCR4-se is a highly sensitive marker of disease activity and a new potential diagnostic and prognostic biomarker in PMF.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32536689</pmid><doi>10.1038/s41375-020-0926-6</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-8357-7192</orcidid><orcidid>https://orcid.org/0000-0002-1862-8168</orcidid></addata></record> |
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| ispartof | Leukemia, 2021-02, Vol.35 (2), p.468-475 |
| issn | 0887-6924 1476-5551 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | 13/21 13/31 45/77 631/67 692/420 Aged Anemia Antigens, CD34 - metabolism Biomarkers Biomarkers - metabolism Blood Blood cancer Blood cells Blood Cells - metabolism Cancer Research Care and treatment Case-Control Studies CD34 antigen Cell death Chemokines Cohort Studies Critical Care Medicine CXCR4 protein Development and progression Diagnosis Diagnostic systems Female Fibrosis Gene expression Genetic aspects Health aspects Hematology Hemoglobin Humans Intensive Internal Medicine Leukopenia Male Medicine Medicine & Public Health Middle Aged Mutation Myelofibrosis Neoplasms Oncology Polycythemia Polycythemia vera Primary Myelofibrosis - diagnosis Primary Myelofibrosis - metabolism Prognosis Receptors, CXCR4 - metabolism Signal Transduction Splenomegaly Survival Rate Thrombocytopenia |
| title | Reduced CXCR4-expression on CD34-positive blood cells predicts outcomes of persons with primary myelofibrosis |
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