ASXL1 mutations are frequent and prognostically detrimental in CSF3R‐mutated chronic neutrophilic leukemia
Colony stimulating factor 3 receptor gene (CSF3R) mutations have recently been associated with chronic neutrophilic leukemia (CNL). Fourteen patients with CSF3R‐mutated CNL (median age 67 years; 57% males) were screened for additional mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mu...
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| Veröffentlicht in: | American journal of hematology 2015-07, Vol.90 (7), p.653-656 |
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| creator | Elliott, Michelle A. Pardanani, Animesh Hanson, Curtis A. Lasho, Terra L. Finke, Christy M. Belachew, Alem A. Tefferi, Ayalew |
| description | Colony stimulating factor 3 receptor gene (CSF3R) mutations have recently been associated with chronic neutrophilic leukemia (CNL). Fourteen patients with CSF3R‐mutated CNL (median age 67 years; 57% males) were screened for additional mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mutation (two patients expressed both), respectively. Two patients developed blastic transformation, both SETBP1‐mutated and ASXL1‐unmutated, whereas two other cases evolved into chronic myelomonocytic leukemia (CMML), both ASXL1‐mutated and SETBP1‐unmutated. Median survival was 23.2 months (10 deaths documented). On multivariable analysis mutated ASXL1 (P = 0.009; HR 19.6, 95% CI 2.1–184.1) and thrombocytopenia (P = 0.005; HR 28.8, 95% CI 2.8–298.2) were independently predictive of shortened survival. This study provides information on the natural history of CSF3R‐mutated CNL and identifies mutant ASXL1 and thrombocytopenia as risk factors for survival. The study also suggests pathogenetic roles for SETBP1 and ASXL1 mutations in disease evolution into blast phase disease and CMML, respectively. Am. J. Hematol. 90:653–656, 2015. © 2015 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/ajh.24031 |
| format | Article |
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Fourteen patients with CSF3R‐mutated CNL (median age 67 years; 57% males) were screened for additional mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mutation (two patients expressed both), respectively. Two patients developed blastic transformation, both SETBP1‐mutated and ASXL1‐unmutated, whereas two other cases evolved into chronic myelomonocytic leukemia (CMML), both ASXL1‐mutated and SETBP1‐unmutated. Median survival was 23.2 months (10 deaths documented). On multivariable analysis mutated ASXL1 (P = 0.009; HR 19.6, 95% CI 2.1–184.1) and thrombocytopenia (P = 0.005; HR 28.8, 95% CI 2.8–298.2) were independently predictive of shortened survival. This study provides information on the natural history of CSF3R‐mutated CNL and identifies mutant ASXL1 and thrombocytopenia as risk factors for survival. The study also suggests pathogenetic roles for SETBP1 and ASXL1 mutations in disease evolution into blast phase disease and CMML, respectively. Am. J. Hematol. 90:653–656, 2015. © 2015 Wiley Periodicals, Inc.</description><identifier>ISSN: 0361-8609</identifier><identifier>EISSN: 1096-8652</identifier><identifier>DOI: 10.1002/ajh.24031</identifier><identifier>PMID: 25850813</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents - therapeutic use ; Carrier Proteins - genetics ; Disease Progression ; Female ; Gene Expression ; Hematology ; Humans ; Leukemia, Myelomonocytic, Chronic - diagnosis ; Leukemia, Myelomonocytic, Chronic - drug therapy ; Leukemia, Myelomonocytic, Chronic - genetics ; Leukemia, Myelomonocytic, Chronic - mortality ; Leukemia, Neutrophilic, Chronic - diagnosis ; Leukemia, Neutrophilic, Chronic - drug therapy ; Leukemia, Neutrophilic, Chronic - genetics ; Leukemia, Neutrophilic, Chronic - mortality ; Male ; Middle Aged ; Mutation ; Nuclear Proteins - genetics ; Prognosis ; Receptors, Colony-Stimulating Factor - genetics ; Repressor Proteins - genetics ; Retrospective Studies ; Risk Factors ; Survival Analysis ; Thrombocytopenia - physiopathology</subject><ispartof>American journal of hematology, 2015-07, Vol.90 (7), p.653-656</ispartof><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4541-2e77c87ee7dbbb1a223bc0cf9cdc271cbbd815357c11917ae23f7a385f8f74433</citedby><cites>FETCH-LOGICAL-c4541-2e77c87ee7dbbb1a223bc0cf9cdc271cbbd815357c11917ae23f7a385f8f74433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fajh.24031$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fajh.24031$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25850813$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elliott, Michelle A.</creatorcontrib><creatorcontrib>Pardanani, Animesh</creatorcontrib><creatorcontrib>Hanson, Curtis A.</creatorcontrib><creatorcontrib>Lasho, Terra L.</creatorcontrib><creatorcontrib>Finke, Christy M.</creatorcontrib><creatorcontrib>Belachew, Alem A.</creatorcontrib><creatorcontrib>Tefferi, Ayalew</creatorcontrib><title>ASXL1 mutations are frequent and prognostically detrimental in CSF3R‐mutated chronic neutrophilic leukemia</title><title>American journal of hematology</title><addtitle>Am J Hematol</addtitle><description>Colony stimulating factor 3 receptor gene (CSF3R) mutations have recently been associated with chronic neutrophilic leukemia (CNL). Fourteen patients with CSF3R‐mutated CNL (median age 67 years; 57% males) were screened for additional mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mutation (two patients expressed both), respectively. Two patients developed blastic transformation, both SETBP1‐mutated and ASXL1‐unmutated, whereas two other cases evolved into chronic myelomonocytic leukemia (CMML), both ASXL1‐mutated and SETBP1‐unmutated. Median survival was 23.2 months (10 deaths documented). On multivariable analysis mutated ASXL1 (P = 0.009; HR 19.6, 95% CI 2.1–184.1) and thrombocytopenia (P = 0.005; HR 28.8, 95% CI 2.8–298.2) were independently predictive of shortened survival. This study provides information on the natural history of CSF3R‐mutated CNL and identifies mutant ASXL1 and thrombocytopenia as risk factors for survival. The study also suggests pathogenetic roles for SETBP1 and ASXL1 mutations in disease evolution into blast phase disease and CMML, respectively. Am. J. Hematol. 90:653–656, 2015. © 2015 Wiley Periodicals, Inc.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Carrier Proteins - genetics</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Hematology</subject><subject>Humans</subject><subject>Leukemia, Myelomonocytic, Chronic - diagnosis</subject><subject>Leukemia, Myelomonocytic, Chronic - drug therapy</subject><subject>Leukemia, Myelomonocytic, Chronic - genetics</subject><subject>Leukemia, Myelomonocytic, Chronic - mortality</subject><subject>Leukemia, Neutrophilic, Chronic - diagnosis</subject><subject>Leukemia, Neutrophilic, Chronic - drug therapy</subject><subject>Leukemia, Neutrophilic, Chronic - genetics</subject><subject>Leukemia, Neutrophilic, Chronic - mortality</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Nuclear Proteins - genetics</subject><subject>Prognosis</subject><subject>Receptors, Colony-Stimulating Factor - genetics</subject><subject>Repressor Proteins - genetics</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Survival Analysis</subject><subject>Thrombocytopenia - physiopathology</subject><issn>0361-8609</issn><issn>1096-8652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFO3DAQhq0KVBbaQ18AWeIChwWPncTOcbWCAloJCVqpt8hxJqy3jrPYiaq99RF4xj5J3V3oAYmTx5pPn2bmJ-QLsHNgjF_o1fKcZ0zABzIBVhZTVeR8j0yYKCDVrDwghzGuGAPIFPtIDniucqZATIibPfxYAO3GQQ-295HqgLQN-DSiH6j2DV2H_tH3cbBGO7ehDQ7BdqmpHbWezh-uxP2f389bATbULEPvraEexyH066V16eNw_Imd1Z_IfqtdxM8v7xH5fnX5bX49Xdx9vZnPFlOT5RlMOUpplESUTV3XoDkXtWGmLU1juART142CXOTSAJQgNXLRSi1U3qpWZpkQR-R0502zp0XiUHU2GnROe-zHWEFRsiJnmSgTevIGXfVj8Gm6LQVSqUIm6mxHmdDHGLCt1ukIOmwqYNW_CKoUQbWNILHHL8ax7rD5T77ePAEXO-CXdbh531TNbq93yr9nTJFs</recordid><startdate>201507</startdate><enddate>201507</enddate><creator>Elliott, Michelle A.</creator><creator>Pardanani, Animesh</creator><creator>Hanson, Curtis A.</creator><creator>Lasho, Terra L.</creator><creator>Finke, Christy M.</creator><creator>Belachew, Alem A.</creator><creator>Tefferi, Ayalew</creator><general>Wiley Subscription Services, Inc</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>K9.</scope><scope>7X8</scope></search><sort><creationdate>201507</creationdate><title>ASXL1 mutations are frequent and prognostically detrimental in CSF3R‐mutated chronic neutrophilic leukemia</title><author>Elliott, Michelle A. ; 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Fourteen patients with CSF3R‐mutated CNL (median age 67 years; 57% males) were screened for additional mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mutation (two patients expressed both), respectively. Two patients developed blastic transformation, both SETBP1‐mutated and ASXL1‐unmutated, whereas two other cases evolved into chronic myelomonocytic leukemia (CMML), both ASXL1‐mutated and SETBP1‐unmutated. Median survival was 23.2 months (10 deaths documented). On multivariable analysis mutated ASXL1 (P = 0.009; HR 19.6, 95% CI 2.1–184.1) and thrombocytopenia (P = 0.005; HR 28.8, 95% CI 2.8–298.2) were independently predictive of shortened survival. This study provides information on the natural history of CSF3R‐mutated CNL and identifies mutant ASXL1 and thrombocytopenia as risk factors for survival. The study also suggests pathogenetic roles for SETBP1 and ASXL1 mutations in disease evolution into blast phase disease and CMML, respectively. Am. J. 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| subjects | Adult Aged Aged, 80 and over Antineoplastic Agents - therapeutic use Carrier Proteins - genetics Disease Progression Female Gene Expression Hematology Humans Leukemia, Myelomonocytic, Chronic - diagnosis Leukemia, Myelomonocytic, Chronic - drug therapy Leukemia, Myelomonocytic, Chronic - genetics Leukemia, Myelomonocytic, Chronic - mortality Leukemia, Neutrophilic, Chronic - diagnosis Leukemia, Neutrophilic, Chronic - drug therapy Leukemia, Neutrophilic, Chronic - genetics Leukemia, Neutrophilic, Chronic - mortality Male Middle Aged Mutation Nuclear Proteins - genetics Prognosis Receptors, Colony-Stimulating Factor - genetics Repressor Proteins - genetics Retrospective Studies Risk Factors Survival Analysis Thrombocytopenia - physiopathology |
| title | ASXL1 mutations are frequent and prognostically detrimental in CSF3R‐mutated chronic neutrophilic leukemia |
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