BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia
Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic (MDS) patients can also improve overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, but reliable biological markers predicting response and OS in patients treated...
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| Veröffentlicht in: | Oncotarget 2017-07, Vol.8 (29), p.47103-47109 |
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| creator | Vidal, Valérie Robert, Guillaume Goursaud, Laure Durand, Laetitia Ginet, Clemence Karsenti, Jean Michel Luciano, Frederic Gastaud, Lauris Garnier, Georges Braun, Thorsten Hirsch, Pierre Raffoux, Emmanuel Nloga, Anne Marie Padua, Rose Ann Dombret, Hervé Rohrlich, Pierre Ades, Lionel Chomienne, Christine Auberger, Patrick Fenaux, Pierre Cluzeau, Thomas |
| description | Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic (MDS) patients can also improve overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, but reliable biological markers predicting response and OS in patients treated with AZA are lacking. In a preliminary study, we found that an increase of the percentage of BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA resistance. In this study, we assessed prospectively by flow cytometry the prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients (42 MDS and 28 AML), prior to AZA treatment.In patients with baseline marrow blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells inversely correlated with response to AZA and OS independently of the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R). Specifically, OS was significantly lower in patients with more than 10% BCL2L10 positive cells (median 8.3 vs 22.9 months in patients with less than 10% positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a biomarker for azacitidine response and OS, with a potential impact in clinical practice. |
| doi_str_mv | 10.18632/oncotarget.17482 |
| format | Article |
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In a preliminary study, we found that an increase of the percentage of BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA resistance. In this study, we assessed prospectively by flow cytometry the prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients (42 MDS and 28 AML), prior to AZA treatment.In patients with baseline marrow blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells inversely correlated with response to AZA and OS independently of the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R). Specifically, OS was significantly lower in patients with more than 10% BCL2L10 positive cells (median 8.3 vs 22.9 months in patients with less than 10% positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a biomarker for azacitidine response and OS, with a potential impact in clinical practice.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.17482</identifier><identifier>PMID: 28514758</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic - therapeutic use ; Azacitidine - therapeutic use ; Biomarkers ; Bone Marrow Cells - metabolism ; Bone Marrow Cells - pathology ; Female ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute - diagnosis ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - metabolism ; Leukemia, Myeloid, Acute - mortality ; Male ; Middle Aged ; Myelodysplastic Syndromes - diagnosis ; Myelodysplastic Syndromes - drug therapy ; Myelodysplastic Syndromes - metabolism ; Myelodysplastic Syndromes - mortality ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Research Paper ; Treatment Outcome</subject><ispartof>Oncotarget, 2017-07, Vol.8 (29), p.47103-47109</ispartof><rights>Copyright: © 2017 Vidal et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c286t-949050c07756bd4a1bee8d51a4ad9fe3fd9b7f9486447e9875d746a03155d0613</citedby><cites>FETCH-LOGICAL-c286t-949050c07756bd4a1bee8d51a4ad9fe3fd9b7f9486447e9875d746a03155d0613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564547/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564547/$$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/28514758$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vidal, Valérie</creatorcontrib><creatorcontrib>Robert, Guillaume</creatorcontrib><creatorcontrib>Goursaud, Laure</creatorcontrib><creatorcontrib>Durand, Laetitia</creatorcontrib><creatorcontrib>Ginet, Clemence</creatorcontrib><creatorcontrib>Karsenti, Jean Michel</creatorcontrib><creatorcontrib>Luciano, Frederic</creatorcontrib><creatorcontrib>Gastaud, Lauris</creatorcontrib><creatorcontrib>Garnier, Georges</creatorcontrib><creatorcontrib>Braun, Thorsten</creatorcontrib><creatorcontrib>Hirsch, Pierre</creatorcontrib><creatorcontrib>Raffoux, Emmanuel</creatorcontrib><creatorcontrib>Nloga, Anne Marie</creatorcontrib><creatorcontrib>Padua, Rose Ann</creatorcontrib><creatorcontrib>Dombret, Hervé</creatorcontrib><creatorcontrib>Rohrlich, Pierre</creatorcontrib><creatorcontrib>Ades, Lionel</creatorcontrib><creatorcontrib>Chomienne, Christine</creatorcontrib><creatorcontrib>Auberger, Patrick</creatorcontrib><creatorcontrib>Fenaux, Pierre</creatorcontrib><creatorcontrib>Cluzeau, Thomas</creatorcontrib><title>BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic (MDS) patients can also improve overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, but reliable biological markers predicting response and OS in patients treated with AZA are lacking. In a preliminary study, we found that an increase of the percentage of BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA resistance. In this study, we assessed prospectively by flow cytometry the prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients (42 MDS and 28 AML), prior to AZA treatment.In patients with baseline marrow blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells inversely correlated with response to AZA and OS independently of the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R). Specifically, OS was significantly lower in patients with more than 10% BCL2L10 positive cells (median 8.3 vs 22.9 months in patients with less than 10% positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a biomarker for azacitidine response and OS, with a potential impact in clinical practice.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antimetabolites, Antineoplastic - therapeutic use</subject><subject>Azacitidine - therapeutic use</subject><subject>Biomarkers</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Bone Marrow Cells - pathology</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Leukemia, Myeloid, Acute - diagnosis</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Leukemia, Myeloid, Acute - mortality</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myelodysplastic Syndromes - diagnosis</subject><subject>Myelodysplastic Syndromes - drug therapy</subject><subject>Myelodysplastic Syndromes - metabolism</subject><subject>Myelodysplastic Syndromes - mortality</subject><subject>Neoplasm Staging</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Research Paper</subject><subject>Treatment Outcome</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUcFu1DAUjBCIVm0_gAvykcsWO7Fj54IEK1qQVuJSztaL_bIYEjvYTqvlS_q59e6WUnywn_xmxp43VfWG0Uum2qZ-H7wJGeIW8yWTXNUvqlPW8W5VC9G8fFafVBcp_aRlCS5V3b2uTmolGJdCnVb3n9abesMomUNy2d0iMTiOiThP-uCRTBBjuCMQkYAvtxZnLJvPZI5h60PKzpABTA6RhIHAHzBFxrpCDUs2YcK91LTDMdhdmkc4ENLO27jvgbcEzJLxCHGWjLj8wsnBefVqgDHhxeN5Vn2_-nyz_rLafLv-uv64WZlatXlVTFJBDZVStL3lwHpEZQUDDrYbsBls18uh46rlXGKnpLCSt0AbJoSlLWvOqg9H3XnpJ7SmWIsw6jm6Yn2nAzj9f8e7H3obbrUQLS8DLQLvHgVi-L1gynpyaT9E8BiWpFlHKWOSSlGg7Ag1MaQUcXh6hlF9CFX_C1UfQi2ct8__98T4G2HzAJrwpH0</recordid><startdate>20170718</startdate><enddate>20170718</enddate><creator>Vidal, Valérie</creator><creator>Robert, Guillaume</creator><creator>Goursaud, Laure</creator><creator>Durand, Laetitia</creator><creator>Ginet, Clemence</creator><creator>Karsenti, Jean Michel</creator><creator>Luciano, Frederic</creator><creator>Gastaud, Lauris</creator><creator>Garnier, Georges</creator><creator>Braun, Thorsten</creator><creator>Hirsch, Pierre</creator><creator>Raffoux, Emmanuel</creator><creator>Nloga, Anne Marie</creator><creator>Padua, Rose Ann</creator><creator>Dombret, Hervé</creator><creator>Rohrlich, Pierre</creator><creator>Ades, Lionel</creator><creator>Chomienne, Christine</creator><creator>Auberger, Patrick</creator><creator>Fenaux, Pierre</creator><creator>Cluzeau, Thomas</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170718</creationdate><title>BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia</title><author>Vidal, Valérie ; Robert, Guillaume ; Goursaud, Laure ; Durand, Laetitia ; Ginet, Clemence ; Karsenti, Jean Michel ; Luciano, Frederic ; Gastaud, Lauris ; Garnier, Georges ; Braun, Thorsten ; Hirsch, Pierre ; Raffoux, Emmanuel ; Nloga, Anne Marie ; Padua, Rose Ann ; Dombret, Hervé ; Rohrlich, Pierre ; Ades, Lionel ; Chomienne, Christine ; Auberger, Patrick ; Fenaux, Pierre ; Cluzeau, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c286t-949050c07756bd4a1bee8d51a4ad9fe3fd9b7f9486447e9875d746a03155d0613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antimetabolites, Antineoplastic - therapeutic use</topic><topic>Azacitidine - therapeutic use</topic><topic>Biomarkers</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Bone Marrow Cells - pathology</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Leukemia, Myeloid, Acute - diagnosis</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Leukemia, Myeloid, Acute - mortality</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myelodysplastic Syndromes - diagnosis</topic><topic>Myelodysplastic Syndromes - drug therapy</topic><topic>Myelodysplastic Syndromes - metabolism</topic><topic>Myelodysplastic Syndromes - mortality</topic><topic>Neoplasm Staging</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Research Paper</topic><topic>Treatment Outcome</topic><toplevel>online_resources</toplevel><creatorcontrib>Vidal, Valérie</creatorcontrib><creatorcontrib>Robert, Guillaume</creatorcontrib><creatorcontrib>Goursaud, Laure</creatorcontrib><creatorcontrib>Durand, Laetitia</creatorcontrib><creatorcontrib>Ginet, Clemence</creatorcontrib><creatorcontrib>Karsenti, Jean Michel</creatorcontrib><creatorcontrib>Luciano, Frederic</creatorcontrib><creatorcontrib>Gastaud, Lauris</creatorcontrib><creatorcontrib>Garnier, Georges</creatorcontrib><creatorcontrib>Braun, Thorsten</creatorcontrib><creatorcontrib>Hirsch, Pierre</creatorcontrib><creatorcontrib>Raffoux, Emmanuel</creatorcontrib><creatorcontrib>Nloga, Anne Marie</creatorcontrib><creatorcontrib>Padua, Rose Ann</creatorcontrib><creatorcontrib>Dombret, Hervé</creatorcontrib><creatorcontrib>Rohrlich, Pierre</creatorcontrib><creatorcontrib>Ades, Lionel</creatorcontrib><creatorcontrib>Chomienne, Christine</creatorcontrib><creatorcontrib>Auberger, Patrick</creatorcontrib><creatorcontrib>Fenaux, Pierre</creatorcontrib><creatorcontrib>Cluzeau, Thomas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vidal, Valérie</au><au>Robert, Guillaume</au><au>Goursaud, Laure</au><au>Durand, Laetitia</au><au>Ginet, Clemence</au><au>Karsenti, Jean Michel</au><au>Luciano, Frederic</au><au>Gastaud, Lauris</au><au>Garnier, Georges</au><au>Braun, Thorsten</au><au>Hirsch, Pierre</au><au>Raffoux, Emmanuel</au><au>Nloga, Anne Marie</au><au>Padua, Rose Ann</au><au>Dombret, Hervé</au><au>Rohrlich, Pierre</au><au>Ades, Lionel</au><au>Chomienne, Christine</au><au>Auberger, Patrick</au><au>Fenaux, Pierre</au><au>Cluzeau, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-07-18</date><risdate>2017</risdate><volume>8</volume><issue>29</issue><spage>47103</spage><epage>47109</epage><pages>47103-47109</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic (MDS) patients can also improve overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, but reliable biological markers predicting response and OS in patients treated with AZA are lacking. In a preliminary study, we found that an increase of the percentage of BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA resistance. In this study, we assessed prospectively by flow cytometry the prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients (42 MDS and 28 AML), prior to AZA treatment.In patients with baseline marrow blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells inversely correlated with response to AZA and OS independently of the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R). Specifically, OS was significantly lower in patients with more than 10% BCL2L10 positive cells (median 8.3 vs 22.9 months in patients with less than 10% positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a biomarker for azacitidine response and OS, with a potential impact in clinical practice.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28514758</pmid><doi>10.18632/oncotarget.17482</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antimetabolites, Antineoplastic - therapeutic use Azacitidine - therapeutic use Biomarkers Bone Marrow Cells - metabolism Bone Marrow Cells - pathology Female Gene Expression Humans Leukemia, Myeloid, Acute - diagnosis Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - metabolism Leukemia, Myeloid, Acute - mortality Male Middle Aged Myelodysplastic Syndromes - diagnosis Myelodysplastic Syndromes - drug therapy Myelodysplastic Syndromes - metabolism Myelodysplastic Syndromes - mortality Neoplasm Staging Prognosis Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Research Paper Treatment Outcome |
| title | BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia |
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