IKZF1 deletions predict a poor prognosis in children with B‐cell progenitor acute lymphoblastic leukemia: A multicenter analysis in Taiwan
Despite current risk‐directed therapy, approximately 15–20% of pediatric patients with acute lymphoblastic leukemia (ALL) have relapses. Recent genome‐wide analyses have identified that an alteration of IKZF1 is associated with very poor outcomes in B‐cell progenitor ALL. In this study, we determine...
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| creator | Yang, Yung‐Li Hung, Chia‐Cheng Chen, Jiann‐Shiuh Lin, Kai‐Hsin Jou, Shiann‐Tarng Hsiao, Chih‐Cheng Sheen, Jiunn‐Ming Cheng, Chao‐Neng Wu, Kang‐Hsi Lin, Shu‐Rung Yu, Sung‐Liang Chen, Hsuan‐Yu Lu, Meng‐Yao Wang, Shih‐Chung Chang, Hsiu‐Hao Lin, Shu‐Wha Su, Yi‐Ning Lin, Dong‐Tsamn |
| description | Despite current risk‐directed therapy, approximately 15–20% of pediatric patients with acute lymphoblastic leukemia (ALL) have relapses. Recent genome‐wide analyses have identified that an alteration of IKZF1 is associated with very poor outcomes in B‐cell progenitor ALL. In this study, we determined the prognostic significance of IKZF1 deletions in patients with childhood ALL. This study analyzed 242 pediatric B‐cell progenitor ALL patients in Taiwan. We developed a simple yet sensitive multiplex quantitative PCR coupled with capillary electrophoresis to accurately determine the allele dose of IKZF1, and high resolution melting was used for mutation screening for all coding exons of IKZF1. Twenty‐six (10.7%) pediatric B‐cell progenitor ALL patients were found to harbor these deletions. Most of the deletions were broader deletions that encompassed exon 3 to exon 6, consistent with previous reports. Genomic sequencing of IKZF1 was carried out in all cases and no point mutations were identified. Patients with IKZF1 deletions had inferior event‐free survival (P |
| doi_str_mv | 10.1111/j.1349-7006.2011.02031.x |
| format | Article |
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Recent genome‐wide analyses have identified that an alteration of IKZF1 is associated with very poor outcomes in B‐cell progenitor ALL. In this study, we determined the prognostic significance of IKZF1 deletions in patients with childhood ALL. This study analyzed 242 pediatric B‐cell progenitor ALL patients in Taiwan. We developed a simple yet sensitive multiplex quantitative PCR coupled with capillary electrophoresis to accurately determine the allele dose of IKZF1, and high resolution melting was used for mutation screening for all coding exons of IKZF1. Twenty‐six (10.7%) pediatric B‐cell progenitor ALL patients were found to harbor these deletions. Most of the deletions were broader deletions that encompassed exon 3 to exon 6, consistent with previous reports. Genomic sequencing of IKZF1 was carried out in all cases and no point mutations were identified. Patients with IKZF1 deletions had inferior event‐free survival (P < 0.001), and overall survival (P = 0.0016). The association between IKZF1 deletions and event‐free survival was independent of age, leukocyte count at presentation, and cytogenetic subtype by multivariate Cox analysis (P = 0.003, hazard ratio = 2.45). This study indicates that detection of IKZF1 deletions upon diagnosis of B‐cell progenitor ALL may help to identify patients at risk of treatment failure. IKZF1 deletions could be incorporated as a new high‐risk prognostic factor in future treatment protocols. To the best of our knowledge, this is the first study to examine the poor prognosis of IKZF1 deletions in an Asian population. (Cancer Sci 2011; 102: 1874–1881)</description><identifier>ISSN: 1347-9032</identifier><identifier>ISSN: 1349-7006</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/j.1349-7006.2011.02031.x</identifier><identifier>PMID: 21740479</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adolescent ; B-Lymphocytes ; Base Sequence ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Genetic Markers ; Hematologic and hematopoietic diseases ; Humans ; Ikaros Transcription Factor - genetics ; Infant ; Infant, Newborn ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Multivariate Analysis ; Original ; Polymorphism, Single Nucleotide ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Prognosis ; Sequence Analysis, DNA ; Sequence Deletion ; Taiwan ; Treatment Failure ; Tumors</subject><ispartof>Cancer science, 2011-10, Vol.102 (10), p.1874-1881</ispartof><rights>2011 Japanese Cancer Association</rights><rights>2015 INIST-CNRS</rights><rights>2011 Japanese Cancer Association.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5071-eae3400b9726ba26764b8055284e2708a20ee0878503b276ae06b0a53cc3aecc3</citedby><cites>FETCH-LOGICAL-c5071-eae3400b9726ba26764b8055284e2708a20ee0878503b276ae06b0a53cc3aecc3</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/PMC11159039/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11159039/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1349-7006.2011.02031.x$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24741269$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21740479$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Yung‐Li</creatorcontrib><creatorcontrib>Hung, Chia‐Cheng</creatorcontrib><creatorcontrib>Chen, Jiann‐Shiuh</creatorcontrib><creatorcontrib>Lin, Kai‐Hsin</creatorcontrib><creatorcontrib>Jou, Shiann‐Tarng</creatorcontrib><creatorcontrib>Hsiao, Chih‐Cheng</creatorcontrib><creatorcontrib>Sheen, Jiunn‐Ming</creatorcontrib><creatorcontrib>Cheng, Chao‐Neng</creatorcontrib><creatorcontrib>Wu, Kang‐Hsi</creatorcontrib><creatorcontrib>Lin, Shu‐Rung</creatorcontrib><creatorcontrib>Yu, Sung‐Liang</creatorcontrib><creatorcontrib>Chen, Hsuan‐Yu</creatorcontrib><creatorcontrib>Lu, Meng‐Yao</creatorcontrib><creatorcontrib>Wang, Shih‐Chung</creatorcontrib><creatorcontrib>Chang, Hsiu‐Hao</creatorcontrib><creatorcontrib>Lin, Shu‐Wha</creatorcontrib><creatorcontrib>Su, Yi‐Ning</creatorcontrib><creatorcontrib>Lin, Dong‐Tsamn</creatorcontrib><title>IKZF1 deletions predict a poor prognosis in children with B‐cell progenitor acute lymphoblastic leukemia: A multicenter analysis in Taiwan</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Despite current risk‐directed therapy, approximately 15–20% of pediatric patients with acute lymphoblastic leukemia (ALL) have relapses. Recent genome‐wide analyses have identified that an alteration of IKZF1 is associated with very poor outcomes in B‐cell progenitor ALL. In this study, we determined the prognostic significance of IKZF1 deletions in patients with childhood ALL. This study analyzed 242 pediatric B‐cell progenitor ALL patients in Taiwan. We developed a simple yet sensitive multiplex quantitative PCR coupled with capillary electrophoresis to accurately determine the allele dose of IKZF1, and high resolution melting was used for mutation screening for all coding exons of IKZF1. Twenty‐six (10.7%) pediatric B‐cell progenitor ALL patients were found to harbor these deletions. Most of the deletions were broader deletions that encompassed exon 3 to exon 6, consistent with previous reports. Genomic sequencing of IKZF1 was carried out in all cases and no point mutations were identified. Patients with IKZF1 deletions had inferior event‐free survival (P < 0.001), and overall survival (P = 0.0016). The association between IKZF1 deletions and event‐free survival was independent of age, leukocyte count at presentation, and cytogenetic subtype by multivariate Cox analysis (P = 0.003, hazard ratio = 2.45). This study indicates that detection of IKZF1 deletions upon diagnosis of B‐cell progenitor ALL may help to identify patients at risk of treatment failure. IKZF1 deletions could be incorporated as a new high‐risk prognostic factor in future treatment protocols. To the best of our knowledge, this is the first study to examine the poor prognosis of IKZF1 deletions in an Asian population. (Cancer Sci 2011; 102: 1874–1881)</description><subject>Adolescent</subject><subject>B-Lymphocytes</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Genetic Markers</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Ikaros Transcription Factor - genetics</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Multivariate Analysis</subject><subject>Original</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - mortality</subject><subject>Prognosis</subject><subject>Sequence Analysis, DNA</subject><subject>Sequence Deletion</subject><subject>Taiwan</subject><subject>Treatment Failure</subject><subject>Tumors</subject><issn>1347-9032</issn><issn>1349-7006</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcGO0zAQhiMEYpeFV0C-IE4tY8eJEySESsXCipU4sFy4WBN3unVx7BIndHvjATjwjDwJTlsWuOGDPfZ883s0f5YxDlOe1rP1lOeyniiAciqA8ykIyPn05k52epu4u4_VpIZcnGQPYlwD5KWs5f3sRHAlQar6NPt-8e7TOWcLctTb4CPbdLSwpmfINiF06RqufYg2MuuZWVm36Mizre1X7NXPbz8MObdnyNs-4WiGnpjbtZtVaBzG3hrmaPhMrcXnbMbawaUn8j0l1qPbHZWv0G7RP8zuLdFFenQ8z7KP56-v5m8nl-_fXMxnlxNTgOITQsolQFMrUTYoSlXKpoKiEJUkoaBCAURQqaqAvBGqRIKyASxyY3KktJ1lLw-6m6FpaTH206HTm8622O10QKv_zXi70tfhq06zL9I866Tw9KjQhS8DxV63No7DQE9hiLrmuRK8EjKR1YE0XYixo-XtNxxGPa7XevRMj57p0Uy9N1PfpNLHf7d5W_jbvQQ8OQIYDbplh97Y-IeTSnJRjtyLA7e1jnb_3YCezz6MUf4LAO6-GQ</recordid><startdate>201110</startdate><enddate>201110</enddate><creator>Yang, Yung‐Li</creator><creator>Hung, Chia‐Cheng</creator><creator>Chen, Jiann‐Shiuh</creator><creator>Lin, Kai‐Hsin</creator><creator>Jou, Shiann‐Tarng</creator><creator>Hsiao, Chih‐Cheng</creator><creator>Sheen, Jiunn‐Ming</creator><creator>Cheng, Chao‐Neng</creator><creator>Wu, Kang‐Hsi</creator><creator>Lin, Shu‐Rung</creator><creator>Yu, Sung‐Liang</creator><creator>Chen, Hsuan‐Yu</creator><creator>Lu, Meng‐Yao</creator><creator>Wang, Shih‐Chung</creator><creator>Chang, Hsiu‐Hao</creator><creator>Lin, Shu‐Wha</creator><creator>Su, Yi‐Ning</creator><creator>Lin, Dong‐Tsamn</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>201110</creationdate><title>IKZF1 deletions predict a poor prognosis in children with B‐cell progenitor acute lymphoblastic leukemia: A multicenter analysis in Taiwan</title><author>Yang, Yung‐Li ; Hung, Chia‐Cheng ; Chen, Jiann‐Shiuh ; Lin, Kai‐Hsin ; Jou, Shiann‐Tarng ; Hsiao, Chih‐Cheng ; Sheen, Jiunn‐Ming ; Cheng, Chao‐Neng ; Wu, Kang‐Hsi ; Lin, Shu‐Rung ; Yu, Sung‐Liang ; Chen, Hsuan‐Yu ; Lu, Meng‐Yao ; Wang, Shih‐Chung ; Chang, Hsiu‐Hao ; Lin, Shu‐Wha ; Su, Yi‐Ning ; Lin, Dong‐Tsamn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5071-eae3400b9726ba26764b8055284e2708a20ee0878503b276ae06b0a53cc3aecc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adolescent</topic><topic>B-Lymphocytes</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Genetic Markers</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Ikaros Transcription Factor - genetics</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Multivariate Analysis</topic><topic>Original</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - mortality</topic><topic>Prognosis</topic><topic>Sequence Analysis, DNA</topic><topic>Sequence Deletion</topic><topic>Taiwan</topic><topic>Treatment Failure</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Yung‐Li</creatorcontrib><creatorcontrib>Hung, Chia‐Cheng</creatorcontrib><creatorcontrib>Chen, Jiann‐Shiuh</creatorcontrib><creatorcontrib>Lin, Kai‐Hsin</creatorcontrib><creatorcontrib>Jou, Shiann‐Tarng</creatorcontrib><creatorcontrib>Hsiao, Chih‐Cheng</creatorcontrib><creatorcontrib>Sheen, Jiunn‐Ming</creatorcontrib><creatorcontrib>Cheng, Chao‐Neng</creatorcontrib><creatorcontrib>Wu, Kang‐Hsi</creatorcontrib><creatorcontrib>Lin, Shu‐Rung</creatorcontrib><creatorcontrib>Yu, Sung‐Liang</creatorcontrib><creatorcontrib>Chen, Hsuan‐Yu</creatorcontrib><creatorcontrib>Lu, Meng‐Yao</creatorcontrib><creatorcontrib>Wang, Shih‐Chung</creatorcontrib><creatorcontrib>Chang, Hsiu‐Hao</creatorcontrib><creatorcontrib>Lin, Shu‐Wha</creatorcontrib><creatorcontrib>Su, Yi‐Ning</creatorcontrib><creatorcontrib>Lin, Dong‐Tsamn</creatorcontrib><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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Yang, Yung‐Li</au><au>Hung, Chia‐Cheng</au><au>Chen, Jiann‐Shiuh</au><au>Lin, Kai‐Hsin</au><au>Jou, Shiann‐Tarng</au><au>Hsiao, Chih‐Cheng</au><au>Sheen, Jiunn‐Ming</au><au>Cheng, Chao‐Neng</au><au>Wu, Kang‐Hsi</au><au>Lin, Shu‐Rung</au><au>Yu, Sung‐Liang</au><au>Chen, Hsuan‐Yu</au><au>Lu, Meng‐Yao</au><au>Wang, Shih‐Chung</au><au>Chang, Hsiu‐Hao</au><au>Lin, Shu‐Wha</au><au>Su, Yi‐Ning</au><au>Lin, Dong‐Tsamn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IKZF1 deletions predict a poor prognosis in children with B‐cell progenitor acute lymphoblastic leukemia: A multicenter analysis in Taiwan</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2011-10</date><risdate>2011</risdate><volume>102</volume><issue>10</issue><spage>1874</spage><epage>1881</epage><pages>1874-1881</pages><issn>1347-9032</issn><issn>1349-7006</issn><eissn>1349-7006</eissn><abstract>Despite current risk‐directed therapy, approximately 15–20% of pediatric patients with acute lymphoblastic leukemia (ALL) have relapses. Recent genome‐wide analyses have identified that an alteration of IKZF1 is associated with very poor outcomes in B‐cell progenitor ALL. In this study, we determined the prognostic significance of IKZF1 deletions in patients with childhood ALL. This study analyzed 242 pediatric B‐cell progenitor ALL patients in Taiwan. We developed a simple yet sensitive multiplex quantitative PCR coupled with capillary electrophoresis to accurately determine the allele dose of IKZF1, and high resolution melting was used for mutation screening for all coding exons of IKZF1. Twenty‐six (10.7%) pediatric B‐cell progenitor ALL patients were found to harbor these deletions. Most of the deletions were broader deletions that encompassed exon 3 to exon 6, consistent with previous reports. Genomic sequencing of IKZF1 was carried out in all cases and no point mutations were identified. Patients with IKZF1 deletions had inferior event‐free survival (P < 0.001), and overall survival (P = 0.0016). The association between IKZF1 deletions and event‐free survival was independent of age, leukocyte count at presentation, and cytogenetic subtype by multivariate Cox analysis (P = 0.003, hazard ratio = 2.45). This study indicates that detection of IKZF1 deletions upon diagnosis of B‐cell progenitor ALL may help to identify patients at risk of treatment failure. IKZF1 deletions could be incorporated as a new high‐risk prognostic factor in future treatment protocols. To the best of our knowledge, this is the first study to examine the poor prognosis of IKZF1 deletions in an Asian population. (Cancer Sci 2011; 102: 1874–1881)</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21740479</pmid><doi>10.1111/j.1349-7006.2011.02031.x</doi><tpages>8</tpages></addata></record> |
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| subjects | Adolescent B-Lymphocytes Base Sequence Biological and medical sciences Biomarkers, Tumor - genetics Child Child, Preschool Disease-Free Survival Female Genetic Markers Hematologic and hematopoietic diseases Humans Ikaros Transcription Factor - genetics Infant Infant, Newborn Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Multivariate Analysis Original Polymorphism, Single Nucleotide Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - mortality Prognosis Sequence Analysis, DNA Sequence Deletion Taiwan Treatment Failure Tumors |
| title | IKZF1 deletions predict a poor prognosis in children with B‐cell progenitor acute lymphoblastic leukemia: A multicenter analysis in Taiwan |
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