High WT1 expression predicted induction chemotherapy failure in acute myeloid leukemia patients with non-favorable cytogenetic risk
The prognostic significance of WT1 expression at diagnosis in acute myeloid leukemia (AML) remains obscure, and subgroup analysis is the way for clarification. We previously reported the results in t (8;21) AML. In this study, 437 consecutive adult AML patients with non-favorable cytogenetic risk we...
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| Veröffentlicht in: | Clinical and experimental medicine 2023-10, Vol.23 (6), p.2629-2638 |
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| description | The prognostic significance of WT1 expression at diagnosis in acute myeloid leukemia (AML) remains obscure, and subgroup analysis is the way for clarification. We previously reported the results in
t
(8;21) AML. In this study, 437 consecutive adult AML patients with non-favorable cytogenetic risk were enrolled. All patients were tested WT1 transcript levels using real-time quantitative PCR at diagnosis; AML-related common fusion genes, KMT2A-PTD, FLT3-ITD, NPM1, CEBPA and TP53 mutations were simultaneously tested. 92.4% of patients overexpressed WT1 compared to normal bone marrow. The existence of FLT3-ITD, NPM1 mutation and the absence of CEBPA biallelic mutation were significantly related to higher WT1 expression. The cutoff value for WT1 was determined by performing receiver operating characteristic curve analysis in regard to complete remission (CR) achievement and was used to categorize patients into low-expression (WT1-L) and high-expression (WT1-H) groups. In the entire cohort, WT1-H was significantly associated with a lower 1-course and 2-course CR rate (
P
0.05). Therefore, high WT1 expression at diagnosis independently predicted induction chemotherapy failure in AML patients with non-favorable cytogenetic risk, and it was related to relapse just within FAB-M5 and KMT2A rearrangement subgroups. |
| doi_str_mv | 10.1007/s10238-023-00995-5 |
| format | Article |
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t
(8;21) AML. In this study, 437 consecutive adult AML patients with non-favorable cytogenetic risk were enrolled. All patients were tested WT1 transcript levels using real-time quantitative PCR at diagnosis; AML-related common fusion genes, KMT2A-PTD, FLT3-ITD, NPM1, CEBPA and TP53 mutations were simultaneously tested. 92.4% of patients overexpressed WT1 compared to normal bone marrow. The existence of FLT3-ITD, NPM1 mutation and the absence of CEBPA biallelic mutation were significantly related to higher WT1 expression. The cutoff value for WT1 was determined by performing receiver operating characteristic curve analysis in regard to complete remission (CR) achievement and was used to categorize patients into low-expression (WT1-L) and high-expression (WT1-H) groups. In the entire cohort, WT1-H was significantly associated with a lower 1-course and 2-course CR rate (
P
< 0.0010 and
P
= 0.0060) but was not related to relapse-free survival (RFS). Multivariate analysis showed that WT1-H was an independent adverse prognostic factor for both 1-course and 2-course CR achievement. Subgroup analysis was further performed. WT1-H had a significant adverse impact on CR achievement within intermediate-cytogenetic risk, high-cytogenetic risk, ELN-defined-intermediate-risk, normal karyotype, KMT2A rearrangement, FAB-M2, FAB-M5 and NPM1 mutation (+) subgroups, whereas it had no impact within ELN-defined-low-risk, ELN-defined-high-risk, FAB-M4, FLT3-ITD mutation (+) and CEBPA biallelic mutation (+) subgroups. Moreover, WT1-H patients had a significantly lower RFS rate than WT1-L patients within both FAB-M5 and KMT2A rearrangement subgroups (
P
= 0.010 and 0.028), whereas WT1 had no impact on RFS within other subgroups mentioned above (all
P
> 0.05). Therefore, high WT1 expression at diagnosis independently predicted induction chemotherapy failure in AML patients with non-favorable cytogenetic risk, and it was related to relapse just within FAB-M5 and KMT2A rearrangement subgroups.</description><identifier>ISSN: 1591-9528</identifier><identifier>ISSN: 1591-8890</identifier><identifier>EISSN: 1591-9528</identifier><identifier>DOI: 10.1007/s10238-023-00995-5</identifier><identifier>PMID: 36637581</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Acute myeloid leukemia ; Chemotherapy ; Cytogenetics ; Diagnosis ; Fusion protein ; Hematology ; Internal Medicine ; Karyotypes ; Leukemia ; Medicine ; Medicine & Public Health ; Multivariate analysis ; Mutation ; Oncology ; p53 Protein ; Remission</subject><ispartof>Clinical and experimental medicine, 2023-10, Vol.23 (6), p.2629-2638</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-e116943bbca848d121b6d761caf4abdecf443ad9777c93ef30654b34b09d12e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10238-023-00995-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10238-023-00995-5$$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/36637581$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Nan</creatorcontrib><creatorcontrib>Chen, Wen-Min</creatorcontrib><creatorcontrib>Li, Ling-Di</creatorcontrib><creatorcontrib>Long, Ling-Yu</creatorcontrib><creatorcontrib>Wang, Xu</creatorcontrib><creatorcontrib>Jiang, Qian</creatorcontrib><creatorcontrib>Jiang, Hao</creatorcontrib><creatorcontrib>Huang, Xiao-Jun</creatorcontrib><creatorcontrib>Qin, Ya-Zhen</creatorcontrib><title>High WT1 expression predicted induction chemotherapy failure in acute myeloid leukemia patients with non-favorable cytogenetic risk</title><title>Clinical and experimental medicine</title><addtitle>Clin Exp Med</addtitle><addtitle>Clin Exp Med</addtitle><description>The prognostic significance of WT1 expression at diagnosis in acute myeloid leukemia (AML) remains obscure, and subgroup analysis is the way for clarification. We previously reported the results in
t
(8;21) AML. In this study, 437 consecutive adult AML patients with non-favorable cytogenetic risk were enrolled. All patients were tested WT1 transcript levels using real-time quantitative PCR at diagnosis; AML-related common fusion genes, KMT2A-PTD, FLT3-ITD, NPM1, CEBPA and TP53 mutations were simultaneously tested. 92.4% of patients overexpressed WT1 compared to normal bone marrow. The existence of FLT3-ITD, NPM1 mutation and the absence of CEBPA biallelic mutation were significantly related to higher WT1 expression. The cutoff value for WT1 was determined by performing receiver operating characteristic curve analysis in regard to complete remission (CR) achievement and was used to categorize patients into low-expression (WT1-L) and high-expression (WT1-H) groups. In the entire cohort, WT1-H was significantly associated with a lower 1-course and 2-course CR rate (
P
< 0.0010 and
P
= 0.0060) but was not related to relapse-free survival (RFS). Multivariate analysis showed that WT1-H was an independent adverse prognostic factor for both 1-course and 2-course CR achievement. Subgroup analysis was further performed. WT1-H had a significant adverse impact on CR achievement within intermediate-cytogenetic risk, high-cytogenetic risk, ELN-defined-intermediate-risk, normal karyotype, KMT2A rearrangement, FAB-M2, FAB-M5 and NPM1 mutation (+) subgroups, whereas it had no impact within ELN-defined-low-risk, ELN-defined-high-risk, FAB-M4, FLT3-ITD mutation (+) and CEBPA biallelic mutation (+) subgroups. Moreover, WT1-H patients had a significantly lower RFS rate than WT1-L patients within both FAB-M5 and KMT2A rearrangement subgroups (
P
= 0.010 and 0.028), whereas WT1 had no impact on RFS within other subgroups mentioned above (all
P
> 0.05). Therefore, high WT1 expression at diagnosis independently predicted induction chemotherapy failure in AML patients with non-favorable cytogenetic risk, and it was related to relapse just within FAB-M5 and KMT2A rearrangement subgroups.</description><subject>Acute myeloid leukemia</subject><subject>Chemotherapy</subject><subject>Cytogenetics</subject><subject>Diagnosis</subject><subject>Fusion protein</subject><subject>Hematology</subject><subject>Internal Medicine</subject><subject>Karyotypes</subject><subject>Leukemia</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Multivariate analysis</subject><subject>Mutation</subject><subject>Oncology</subject><subject>p53 Protein</subject><subject>Remission</subject><issn>1591-9528</issn><issn>1591-8890</issn><issn>1591-9528</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kU1vFSEUhonR2Fr9Ay4MiRs3Y_kYYGZpmmpNmripcUkYOHMv7QyMwGjvun-83N76ERduDiec5zyQvAi9puQ9JUSdZkoY75paGkL6XjTiCTqmoqdNL1j39K_-CL3I-ZoQKjpOnqMjLiVXoqPH6O7Cb7b42xXFcLskyNnHgGvjvC3gsA9utWV_Z7cwx7KFZJYdHo2f1gR1jI1dC-B5B1P0Dk-w3sDsDV5M8RBKxj992eIQQzOaHzGZYQJsdyVuIEDxFiefb16iZ6OZMrx6PE_Q14_nV2cXzeWXT5_PPlw2ljNZGqBU9i0fBmu6tnOU0UE6Jak1Y2sGB3ZsW25cr5SyPYeREynagbcD6SsMjJ-gdwfvkuL3FXLRs88WpskEiGvWTEmhqpCqir79B72Oawr1d5p1iijWdnIvZAfKpphzglEvyc8m7TQleh-RPkSka9EPEWlRl948qtdhBvd75VcmFeAHINdR2ED68_Z_tPfPUZ6s</recordid><startdate>20231001</startdate><enddate>20231001</enddate><creator>Xu, Nan</creator><creator>Chen, Wen-Min</creator><creator>Li, Ling-Di</creator><creator>Long, Ling-Yu</creator><creator>Wang, Xu</creator><creator>Jiang, Qian</creator><creator>Jiang, Hao</creator><creator>Huang, Xiao-Jun</creator><creator>Qin, Ya-Zhen</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20231001</creationdate><title>High WT1 expression predicted induction chemotherapy failure in acute myeloid leukemia patients with non-favorable cytogenetic risk</title><author>Xu, Nan ; Chen, Wen-Min ; Li, Ling-Di ; Long, Ling-Yu ; Wang, Xu ; Jiang, Qian ; Jiang, Hao ; Huang, Xiao-Jun ; Qin, Ya-Zhen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-e116943bbca848d121b6d761caf4abdecf443ad9777c93ef30654b34b09d12e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acute myeloid leukemia</topic><topic>Chemotherapy</topic><topic>Cytogenetics</topic><topic>Diagnosis</topic><topic>Fusion protein</topic><topic>Hematology</topic><topic>Internal Medicine</topic><topic>Karyotypes</topic><topic>Leukemia</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Multivariate analysis</topic><topic>Mutation</topic><topic>Oncology</topic><topic>p53 Protein</topic><topic>Remission</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Nan</creatorcontrib><creatorcontrib>Chen, Wen-Min</creatorcontrib><creatorcontrib>Li, Ling-Di</creatorcontrib><creatorcontrib>Long, Ling-Yu</creatorcontrib><creatorcontrib>Wang, Xu</creatorcontrib><creatorcontrib>Jiang, Qian</creatorcontrib><creatorcontrib>Jiang, Hao</creatorcontrib><creatorcontrib>Huang, Xiao-Jun</creatorcontrib><creatorcontrib>Qin, Ya-Zhen</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical and experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Nan</au><au>Chen, Wen-Min</au><au>Li, Ling-Di</au><au>Long, Ling-Yu</au><au>Wang, Xu</au><au>Jiang, Qian</au><au>Jiang, Hao</au><au>Huang, Xiao-Jun</au><au>Qin, Ya-Zhen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High WT1 expression predicted induction chemotherapy failure in acute myeloid leukemia patients with non-favorable cytogenetic risk</atitle><jtitle>Clinical and experimental medicine</jtitle><stitle>Clin Exp Med</stitle><addtitle>Clin Exp Med</addtitle><date>2023-10-01</date><risdate>2023</risdate><volume>23</volume><issue>6</issue><spage>2629</spage><epage>2638</epage><pages>2629-2638</pages><issn>1591-9528</issn><issn>1591-8890</issn><eissn>1591-9528</eissn><abstract>The prognostic significance of WT1 expression at diagnosis in acute myeloid leukemia (AML) remains obscure, and subgroup analysis is the way for clarification. We previously reported the results in
t
(8;21) AML. In this study, 437 consecutive adult AML patients with non-favorable cytogenetic risk were enrolled. All patients were tested WT1 transcript levels using real-time quantitative PCR at diagnosis; AML-related common fusion genes, KMT2A-PTD, FLT3-ITD, NPM1, CEBPA and TP53 mutations were simultaneously tested. 92.4% of patients overexpressed WT1 compared to normal bone marrow. The existence of FLT3-ITD, NPM1 mutation and the absence of CEBPA biallelic mutation were significantly related to higher WT1 expression. The cutoff value for WT1 was determined by performing receiver operating characteristic curve analysis in regard to complete remission (CR) achievement and was used to categorize patients into low-expression (WT1-L) and high-expression (WT1-H) groups. In the entire cohort, WT1-H was significantly associated with a lower 1-course and 2-course CR rate (
P
< 0.0010 and
P
= 0.0060) but was not related to relapse-free survival (RFS). Multivariate analysis showed that WT1-H was an independent adverse prognostic factor for both 1-course and 2-course CR achievement. Subgroup analysis was further performed. WT1-H had a significant adverse impact on CR achievement within intermediate-cytogenetic risk, high-cytogenetic risk, ELN-defined-intermediate-risk, normal karyotype, KMT2A rearrangement, FAB-M2, FAB-M5 and NPM1 mutation (+) subgroups, whereas it had no impact within ELN-defined-low-risk, ELN-defined-high-risk, FAB-M4, FLT3-ITD mutation (+) and CEBPA biallelic mutation (+) subgroups. Moreover, WT1-H patients had a significantly lower RFS rate than WT1-L patients within both FAB-M5 and KMT2A rearrangement subgroups (
P
= 0.010 and 0.028), whereas WT1 had no impact on RFS within other subgroups mentioned above (all
P
> 0.05). Therefore, high WT1 expression at diagnosis independently predicted induction chemotherapy failure in AML patients with non-favorable cytogenetic risk, and it was related to relapse just within FAB-M5 and KMT2A rearrangement subgroups.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>36637581</pmid><doi>10.1007/s10238-023-00995-5</doi><tpages>10</tpages></addata></record> |
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| subjects | Acute myeloid leukemia Chemotherapy Cytogenetics Diagnosis Fusion protein Hematology Internal Medicine Karyotypes Leukemia Medicine Medicine & Public Health Multivariate analysis Mutation Oncology p53 Protein Remission |
| title | High WT1 expression predicted induction chemotherapy failure in acute myeloid leukemia patients with non-favorable cytogenetic risk |
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