A genome-wide single-nucleotide polymorphism-array can improve the prognostic stratification of the core binding factor acute myeloid leukemia

Core binding factor (CBF) AML with the D816 C‐KIT gene mutation demonstrate inferior treatment outcomes. However, the remaining cases without the D816 C‐KIT mutation imply a requirement of more sophisticated dissection of the patients according to their prognosis. In this study, we analyzed the prog...

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Veröffentlicht in:American journal of hematology 2012-10, Vol.87 (10), p.961-968
Hauptverfasser: Huh, Jungwon, Kim, Hee-Je, Jung, Chul Won, Kim, Hee-Jin, Kim, Sun-Hee, Kim, Yeo-Kyeoung, Kim, Hyeoung-Joon, Shin, Myung Geun, Moon, Joon Ho, Sohn, Sang Kyun, Kim, Sung Hyun, Lee, Won Sik, Won, Jong Ho, Mun, Yeung Chul, Kim, Hawk, Park, Jinny, Min, Woo Sung, Kim, Dong Hwan (Dennis)
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container_end_page 968
container_issue 10
container_start_page 961
container_title American journal of hematology
container_volume 87
creator Huh, Jungwon
Kim, Hee-Je
Jung, Chul Won
Kim, Hee-Jin
Kim, Sun-Hee
Kim, Yeo-Kyeoung
Kim, Hyeoung-Joon
Shin, Myung Geun
Moon, Joon Ho
Sohn, Sang Kyun
Kim, Sung Hyun
Lee, Won Sik
Won, Jong Ho
Mun, Yeung Chul
Kim, Hawk
Park, Jinny
Min, Woo Sung
Kim, Dong Hwan (Dennis)
description Core binding factor (CBF) AML with the D816 C‐KIT gene mutation demonstrate inferior treatment outcomes. However, the remaining cases without the D816 C‐KIT mutation imply a requirement of more sophisticated dissection of the patients according to their prognosis. In this study, we analyzed the prognostic value of a single nucleotide polymorphism array (SNP‐A) based karyotyping combined with metaphase cytogenetics (MC) to facilitate further stratification of CBF AML patients. A total of 98 CBF AML patients were included and genome‐wide Human SNP 6.0 Arrays (Affymetrix) were performed using marrow samples taken at diagnosis. Overall, 40 abnormal lesions were identified in 25 patients (26%). Survival of the patients with the abnormal lesion(s) detected by SNP‐A and/or MC was worse than those without lesions in terms of the 2‐year overall survival (OS; 57.5% vs. 76.4%, P = 0.028), event‐free (EFS; 45.7% vs. 66.2%, P = 0.072), and leukemia‐free survival (LFS; 49.0% vs. 77.4%, P = 0.015), specially in the subgroup with inv(16)/t(16;16) (40.9% vs. 80.2% OS, P = 0.040) and in the subgroup without the D816 C‐KIT mutation (61.6% vs. 82.7% OS, P = 0.038). Multivariate analysis confirmed the prognostic impact of the abnormal SNP‐A and/or MC lesion on EFS (HR 2.011, P = 0.047), and LFS (HR 3.231, P = 0.005) in the overall CBF AML. This study suggests that the combined use of SNP‐A with MC in the CBF AML can provide important prognostic value, especially in the inv(16)/t(16;16) subgroup or in the patients without the D816 C‐KIT mutation. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.
doi_str_mv 10.1002/ajh.23281
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However, the remaining cases without the D816 C‐KIT mutation imply a requirement of more sophisticated dissection of the patients according to their prognosis. In this study, we analyzed the prognostic value of a single nucleotide polymorphism array (SNP‐A) based karyotyping combined with metaphase cytogenetics (MC) to facilitate further stratification of CBF AML patients. A total of 98 CBF AML patients were included and genome‐wide Human SNP 6.0 Arrays (Affymetrix) were performed using marrow samples taken at diagnosis. Overall, 40 abnormal lesions were identified in 25 patients (26%). Survival of the patients with the abnormal lesion(s) detected by SNP‐A and/or MC was worse than those without lesions in terms of the 2‐year overall survival (OS; 57.5% vs. 76.4%, P = 0.028), event‐free (EFS; 45.7% vs. 66.2%, P = 0.072), and leukemia‐free survival (LFS; 49.0% vs. 77.4%, P = 0.015), specially in the subgroup with inv(16)/t(16;16) (40.9% vs. 80.2% OS, P = 0.040) and in the subgroup without the D816 C‐KIT mutation (61.6% vs. 82.7% OS, P = 0.038). Multivariate analysis confirmed the prognostic impact of the abnormal SNP‐A and/or MC lesion on EFS (HR 2.011, P = 0.047), and LFS (HR 3.231, P = 0.005) in the overall CBF AML. This study suggests that the combined use of SNP‐A with MC in the CBF AML can provide important prognostic value, especially in the inv(16)/t(16;16) subgroup or in the patients without the D816 C‐KIT mutation. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.</description><identifier>ISSN: 0361-8609</identifier><identifier>EISSN: 1096-8652</identifier><identifier>DOI: 10.1002/ajh.23281</identifier><identifier>PMID: 22886749</identifier><identifier>CODEN: AJHEDD</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Acute Disease ; Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Chromosome Inversion ; Core Binding Factors - genetics ; Cytarabine - administration &amp; dosage ; Cytarabine - analogs &amp; derivatives ; Disease-Free Survival ; Female ; Genome-Wide Association Study ; Hematologic and hematopoietic diseases ; Hematology ; Humans ; Idarubicin - administration &amp; dosage ; Kaplan-Meier Estimate ; Karyotyping ; Leukemia, Myeloid - drug therapy ; Leukemia, Myeloid - genetics ; Leukemia, Myeloid - mortality ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; Neoplasm Proteins - genetics ; Polymorphism, Single Nucleotide ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-kit - genetics ; Remission Induction ; Translocation, Genetic ; Young Adult</subject><ispartof>American journal of hematology, 2012-10, Vol.87 (10), p.961-968</ispartof><rights>Copyright © 2012 Wiley Periodicals, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4211-b0cf3c6f6ed969fcd1c0dc7ae248726a5e955e7ce495fae18d5bc387badaa9d83</citedby><cites>FETCH-LOGICAL-c4211-b0cf3c6f6ed969fcd1c0dc7ae248726a5e955e7ce495fae18d5bc387badaa9d83</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.23281$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fajh.23281$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=26395790$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22886749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huh, Jungwon</creatorcontrib><creatorcontrib>Kim, Hee-Je</creatorcontrib><creatorcontrib>Jung, Chul Won</creatorcontrib><creatorcontrib>Kim, Hee-Jin</creatorcontrib><creatorcontrib>Kim, Sun-Hee</creatorcontrib><creatorcontrib>Kim, Yeo-Kyeoung</creatorcontrib><creatorcontrib>Kim, Hyeoung-Joon</creatorcontrib><creatorcontrib>Shin, Myung Geun</creatorcontrib><creatorcontrib>Moon, Joon Ho</creatorcontrib><creatorcontrib>Sohn, Sang Kyun</creatorcontrib><creatorcontrib>Kim, Sung Hyun</creatorcontrib><creatorcontrib>Lee, Won Sik</creatorcontrib><creatorcontrib>Won, Jong Ho</creatorcontrib><creatorcontrib>Mun, Yeung Chul</creatorcontrib><creatorcontrib>Kim, Hawk</creatorcontrib><creatorcontrib>Park, Jinny</creatorcontrib><creatorcontrib>Min, Woo Sung</creatorcontrib><creatorcontrib>Kim, Dong Hwan (Dennis)</creatorcontrib><creatorcontrib>AML/MDS working party, Korean Society of Hematology</creatorcontrib><creatorcontrib>on behalf of AML/MDS working party, Korean Society of Hematology</creatorcontrib><title>A genome-wide single-nucleotide polymorphism-array can improve the prognostic stratification of the core binding factor acute myeloid leukemia</title><title>American journal of hematology</title><addtitle>Am. J. Hematol</addtitle><description>Core binding factor (CBF) AML with the D816 C‐KIT gene mutation demonstrate inferior treatment outcomes. However, the remaining cases without the D816 C‐KIT mutation imply a requirement of more sophisticated dissection of the patients according to their prognosis. In this study, we analyzed the prognostic value of a single nucleotide polymorphism array (SNP‐A) based karyotyping combined with metaphase cytogenetics (MC) to facilitate further stratification of CBF AML patients. A total of 98 CBF AML patients were included and genome‐wide Human SNP 6.0 Arrays (Affymetrix) were performed using marrow samples taken at diagnosis. Overall, 40 abnormal lesions were identified in 25 patients (26%). Survival of the patients with the abnormal lesion(s) detected by SNP‐A and/or MC was worse than those without lesions in terms of the 2‐year overall survival (OS; 57.5% vs. 76.4%, P = 0.028), event‐free (EFS; 45.7% vs. 66.2%, P = 0.072), and leukemia‐free survival (LFS; 49.0% vs. 77.4%, P = 0.015), specially in the subgroup with inv(16)/t(16;16) (40.9% vs. 80.2% OS, P = 0.040) and in the subgroup without the D816 C‐KIT mutation (61.6% vs. 82.7% OS, P = 0.038). Multivariate analysis confirmed the prognostic impact of the abnormal SNP‐A and/or MC lesion on EFS (HR 2.011, P = 0.047), and LFS (HR 3.231, P = 0.005) in the overall CBF AML. This study suggests that the combined use of SNP‐A with MC in the CBF AML can provide important prognostic value, especially in the inv(16)/t(16;16) subgroup or in the patients without the D816 C‐KIT mutation. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.</description><subject>Acute Disease</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Chromosome Inversion</subject><subject>Core Binding Factors - genetics</subject><subject>Cytarabine - administration &amp; dosage</subject><subject>Cytarabine - analogs &amp; derivatives</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Genome-Wide Association Study</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Humans</subject><subject>Idarubicin - administration &amp; dosage</subject><subject>Kaplan-Meier Estimate</subject><subject>Karyotyping</subject><subject>Leukemia, Myeloid - drug therapy</subject><subject>Leukemia, Myeloid - genetics</subject><subject>Leukemia, Myeloid - mortality</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Proto-Oncogene Proteins c-kit - genetics</subject><subject>Remission Induction</subject><subject>Translocation, Genetic</subject><subject>Young Adult</subject><issn>0361-8609</issn><issn>1096-8652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10d1qFDEUB_BBFLutXvgCEhChXkybzEc-LpdFW6VUBEXwJpxJzuxmOzPZJjPWfQmf2Wx3W0HwJgnhd_7nwMmyV4yeMUqLc1ivzoqykOxJNmNU8VzyuniazWjJWXpTdZQdx7imlLFK0ufZUVFIyUWlZtnvOVni4HvM75xFEt2w7DAfJtOhH3c_G99tex82Kxf7HEKALTEwENdvgv-JZFwlEvxy8HF0hsQxwOhaZ9LpB-Lbe2B8QNK4waZ00oIZfSBgphFJv8XOO0s6nG6wd_Aie9ZCF_Hl4T7Jvn14_3VxmV99vvi4mF_lpioYyxtq2tLwlqNVXLXGMkOtEYBFJUXBoUZV1ygMVqpuAZm0dWNKKRqwAMrK8iQ73eem2W8njKPuXTTYdTCgn6JmVFSC79ISffMPXfspDGk6zWrGq1oIUST1bq9M8DEGbPUmuB7CNkXp3ZJ0WpK-X1Kyrw-JU9OjfZQPW0ng7QFANNC1AQbj4l_HS1ULRZM737s71-H2_x31_NPlQ-t8X-HiiL8eKyDcaC5KUevv1xdaXS_KLwv6Q8vyD8OQuvI</recordid><startdate>201210</startdate><enddate>201210</enddate><creator>Huh, Jungwon</creator><creator>Kim, Hee-Je</creator><creator>Jung, Chul Won</creator><creator>Kim, Hee-Jin</creator><creator>Kim, Sun-Hee</creator><creator>Kim, Yeo-Kyeoung</creator><creator>Kim, Hyeoung-Joon</creator><creator>Shin, Myung Geun</creator><creator>Moon, Joon Ho</creator><creator>Sohn, Sang Kyun</creator><creator>Kim, Sung Hyun</creator><creator>Lee, Won Sik</creator><creator>Won, Jong Ho</creator><creator>Mun, Yeung Chul</creator><creator>Kim, Hawk</creator><creator>Park, Jinny</creator><creator>Min, Woo Sung</creator><creator>Kim, Dong Hwan (Dennis)</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>K9.</scope><scope>7X8</scope></search><sort><creationdate>201210</creationdate><title>A genome-wide single-nucleotide polymorphism-array can improve the prognostic stratification of the core binding factor acute myeloid leukemia</title><author>Huh, Jungwon ; Kim, Hee-Je ; Jung, Chul Won ; Kim, Hee-Jin ; Kim, Sun-Hee ; Kim, Yeo-Kyeoung ; Kim, Hyeoung-Joon ; Shin, Myung Geun ; Moon, Joon Ho ; Sohn, Sang Kyun ; Kim, Sung Hyun ; Lee, Won Sik ; Won, Jong Ho ; Mun, Yeung Chul ; Kim, Hawk ; Park, Jinny ; Min, Woo Sung ; Kim, Dong Hwan (Dennis)</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4211-b0cf3c6f6ed969fcd1c0dc7ae248726a5e955e7ce495fae18d5bc387badaa9d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acute Disease</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Chromosome Inversion</topic><topic>Core Binding Factors - genetics</topic><topic>Cytarabine - administration &amp; dosage</topic><topic>Cytarabine - analogs &amp; derivatives</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Genome-Wide Association Study</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Humans</topic><topic>Idarubicin - administration &amp; dosage</topic><topic>Kaplan-Meier Estimate</topic><topic>Karyotyping</topic><topic>Leukemia, Myeloid - drug therapy</topic><topic>Leukemia, Myeloid - genetics</topic><topic>Leukemia, Myeloid - mortality</topic><topic>Leukemias. 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Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Proto-Oncogene Proteins c-kit - genetics</topic><topic>Remission Induction</topic><topic>Translocation, Genetic</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huh, Jungwon</creatorcontrib><creatorcontrib>Kim, Hee-Je</creatorcontrib><creatorcontrib>Jung, Chul Won</creatorcontrib><creatorcontrib>Kim, Hee-Jin</creatorcontrib><creatorcontrib>Kim, Sun-Hee</creatorcontrib><creatorcontrib>Kim, Yeo-Kyeoung</creatorcontrib><creatorcontrib>Kim, Hyeoung-Joon</creatorcontrib><creatorcontrib>Shin, Myung Geun</creatorcontrib><creatorcontrib>Moon, Joon Ho</creatorcontrib><creatorcontrib>Sohn, Sang Kyun</creatorcontrib><creatorcontrib>Kim, Sung Hyun</creatorcontrib><creatorcontrib>Lee, Won Sik</creatorcontrib><creatorcontrib>Won, Jong Ho</creatorcontrib><creatorcontrib>Mun, Yeung Chul</creatorcontrib><creatorcontrib>Kim, Hawk</creatorcontrib><creatorcontrib>Park, Jinny</creatorcontrib><creatorcontrib>Min, Woo Sung</creatorcontrib><creatorcontrib>Kim, Dong Hwan (Dennis)</creatorcontrib><creatorcontrib>AML/MDS working party, Korean Society of Hematology</creatorcontrib><creatorcontrib>on behalf of AML/MDS working party, Korean Society of Hematology</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huh, Jungwon</au><au>Kim, Hee-Je</au><au>Jung, Chul Won</au><au>Kim, Hee-Jin</au><au>Kim, Sun-Hee</au><au>Kim, Yeo-Kyeoung</au><au>Kim, Hyeoung-Joon</au><au>Shin, Myung Geun</au><au>Moon, Joon Ho</au><au>Sohn, Sang Kyun</au><au>Kim, Sung Hyun</au><au>Lee, Won Sik</au><au>Won, Jong Ho</au><au>Mun, Yeung Chul</au><au>Kim, Hawk</au><au>Park, Jinny</au><au>Min, Woo Sung</au><au>Kim, Dong Hwan (Dennis)</au><aucorp>AML/MDS working party, Korean Society of Hematology</aucorp><aucorp>on behalf of AML/MDS working party, Korean Society of Hematology</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A genome-wide single-nucleotide polymorphism-array can improve the prognostic stratification of the core binding factor acute myeloid leukemia</atitle><jtitle>American journal of hematology</jtitle><addtitle>Am. J. Hematol</addtitle><date>2012-10</date><risdate>2012</risdate><volume>87</volume><issue>10</issue><spage>961</spage><epage>968</epage><pages>961-968</pages><issn>0361-8609</issn><eissn>1096-8652</eissn><coden>AJHEDD</coden><abstract>Core binding factor (CBF) AML with the D816 C‐KIT gene mutation demonstrate inferior treatment outcomes. However, the remaining cases without the D816 C‐KIT mutation imply a requirement of more sophisticated dissection of the patients according to their prognosis. In this study, we analyzed the prognostic value of a single nucleotide polymorphism array (SNP‐A) based karyotyping combined with metaphase cytogenetics (MC) to facilitate further stratification of CBF AML patients. A total of 98 CBF AML patients were included and genome‐wide Human SNP 6.0 Arrays (Affymetrix) were performed using marrow samples taken at diagnosis. Overall, 40 abnormal lesions were identified in 25 patients (26%). Survival of the patients with the abnormal lesion(s) detected by SNP‐A and/or MC was worse than those without lesions in terms of the 2‐year overall survival (OS; 57.5% vs. 76.4%, P = 0.028), event‐free (EFS; 45.7% vs. 66.2%, P = 0.072), and leukemia‐free survival (LFS; 49.0% vs. 77.4%, P = 0.015), specially in the subgroup with inv(16)/t(16;16) (40.9% vs. 80.2% OS, P = 0.040) and in the subgroup without the D816 C‐KIT mutation (61.6% vs. 82.7% OS, P = 0.038). Multivariate analysis confirmed the prognostic impact of the abnormal SNP‐A and/or MC lesion on EFS (HR 2.011, P = 0.047), and LFS (HR 3.231, P = 0.005) in the overall CBF AML. This study suggests that the combined use of SNP‐A with MC in the CBF AML can provide important prognostic value, especially in the inv(16)/t(16;16) subgroup or in the patients without the D816 C‐KIT mutation. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>22886749</pmid><doi>10.1002/ajh.23281</doi><tpages>8</tpages></addata></record>
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subjects Acute Disease
Adolescent
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Chromosome Inversion
Core Binding Factors - genetics
Cytarabine - administration & dosage
Cytarabine - analogs & derivatives
Disease-Free Survival
Female
Genome-Wide Association Study
Hematologic and hematopoietic diseases
Hematology
Humans
Idarubicin - administration & dosage
Kaplan-Meier Estimate
Karyotyping
Leukemia, Myeloid - drug therapy
Leukemia, Myeloid - genetics
Leukemia, Myeloid - mortality
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Middle Aged
Neoplasm Proteins - genetics
Polymorphism, Single Nucleotide
Prognosis
Proportional Hazards Models
Proto-Oncogene Proteins c-kit - genetics
Remission Induction
Translocation, Genetic
Young Adult
title A genome-wide single-nucleotide polymorphism-array can improve the prognostic stratification of the core binding factor acute myeloid leukemia
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