Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study on Patients with Acute Myeloid Leukemia
Background: Recently, whole exome sequencing has been used for the next-generation sequencing of acute myeloid leukemia (AML), and certain gene mutations have been identified in patients with AML. The treatment strategies for leukemia have undergone drastic changes with the rapid development of new...
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| Veröffentlicht in: | Blood 2021-11, Vol.138 (Supplement 1), p.4457-4457 |
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| creator | Hosono, Naoko Yamauchi, Takahiro Chi, SungGi Fukushima, Kentaro Shibayama, Hirohiko Katagiri, Seiichiro Gotoh, Akihiko Eguchi, Motoki Morishita, Takanobu Ogasawara, Reiki Kondo, Takeshi Yanada, Masamitsu Yamamoto, Kazuhito Kobayashi, Tsutomu Kuroda, Junya Usuki, Kensuke Utsu, Yoshikazu Aotsuka, Nobuyuki Yoshimitsu, Makoto Ishitsuka, Kenji Ono, Takaaki Takahashi, Naoto Iyama, Satoshi Nakamura, Makoto Nakamura, Yukinori Fukuhara, Suguru Izutsu, Koji Yamauchi, Nobuhiko Yuda, Junichiro Minami, Yosuke |
| description | Background: Recently, whole exome sequencing has been used for the next-generation sequencing of acute myeloid leukemia (AML), and certain gene mutations have been identified in patients with AML. The treatment strategies for leukemia have undergone drastic changes with the rapid development of new drugs. However, the proper use of newly developed agents poses a major challenge in AML treatment. Genome profiling analysis can be used to select the optimal treatment for patients with newly diagnosed AML.
Methods and Results: Hematologic malignancies (HM)-SCREEN-Japan 01 is an actionable mutation profiling multicenter study of patients with newly diagnosed AML who cannot be treated with first standard treatment or patients who have relapsed/refractory AML (R/R-AML). The objective of this study was to evaluate the frequency and characteristics of cancer-related genomic alterations in patients with AML using a comprehensive genome profiling assay (FoundationOne®Heme (F1H)) and determine the quality of specimens used in gene analysis. Before participant recruitment, approval was obtained from the institutional review board at each participating institution. The trial was registered in the UMIN Clinical Trials Registry (UMIN000035233).
This study was conducted at 17 participating institutions and had a sample size of 200. The eligibility criteria were as follows: 1) histological diagnosis of AML through bone marrow aspiration; 2) fulfillment of either of the following conditions: i) newly diagnosed AML unfit for standard treatment (ND-unfit AML) or ii) R/R-AML; 3) sufficient sample collection via bone marrow aspiration; 4) Age of participants 20 years or above during registration; 5) provision of written informed consent by participants. The primary outcome was the frequency of each genomic alteration, as determined using F1H, which is a comprehensive genome profiling test based on next-generation sequencing, in the AML specimens. The secondary outcome was the association between each genomic alteration and the clinicopathological characteristics, prognosis, and quality of specimens used in the genetic analysis. Serial genome profiling analyses were performed to evaluate the time-dependent changes in the genome profiles of patients administered FLT3 inhibitors, gilteritinib, and quizartinib for treating AML.
One hundred and eighty-two patients were recruited, and the F1H report was successfully obtained for 177 patients (97.3%). The median age of the 66 patients |
| doi_str_mv | 10.1182/blood-2021-149960 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1182_blood_2021_149960</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497121063643</els_id><sourcerecordid>S0006497121063643</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1850-d93f37e45edc1c473d8cba0dcceeb9165038ed9fb791c293fc7246f1ac76f68b3</originalsourceid><addsrcrecordid>eNp9kE1LAzEQhoMoWKs_wFuOeogm2W89FVGrtChUzyE7ma3RbVKyWaUH_7tb69nTwDvvMwwPIaeCXwhRysu69d4wyaVgIq2qnO-RkchkyTiXfJ-MOOc5S6tCHJKjrnvnXKSJzEbke4orHX3rlxboXLd26bQDix09m87P2QIComOPeq0d5eKKTui8jzpa7-hz8I1trVsOURstoIsY6CL2ZkO366E1RB39svGNTqCPSOcbbL01dIb9B66sPiYHjW47PPmbY_J6d_tyM2Wzp_uHm8mMgSgzzkyVNEmBaYYGBKRFYkqoNTcAiHUl8ownJZqqqYtKgBzKUMg0b4SGIm_ysk7GROzuQvBdF7BR62BXOmyU4GrrT_36U1t_audvYK53DA6PfVoMqhu8OEBjA0JUxtt_6B-Z1Hn7</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study on Patients with Acute Myeloid Leukemia</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Hosono, Naoko ; Yamauchi, Takahiro ; Chi, SungGi ; Fukushima, Kentaro ; Shibayama, Hirohiko ; Katagiri, Seiichiro ; Gotoh, Akihiko ; Eguchi, Motoki ; Morishita, Takanobu ; Ogasawara, Reiki ; Kondo, Takeshi ; Yanada, Masamitsu ; Yamamoto, Kazuhito ; Kobayashi, Tsutomu ; Kuroda, Junya ; Usuki, Kensuke ; Utsu, Yoshikazu ; Aotsuka, Nobuyuki ; Yoshimitsu, Makoto ; Ishitsuka, Kenji ; Ono, Takaaki ; Takahashi, Naoto ; Iyama, Satoshi ; Nakamura, Makoto ; Nakamura, Yukinori ; Fukuhara, Suguru ; Izutsu, Koji ; Yamauchi, Nobuhiko ; Yuda, Junichiro ; Minami, Yosuke</creator><creatorcontrib>Hosono, Naoko ; Yamauchi, Takahiro ; Chi, SungGi ; Fukushima, Kentaro ; Shibayama, Hirohiko ; Katagiri, Seiichiro ; Gotoh, Akihiko ; Eguchi, Motoki ; Morishita, Takanobu ; Ogasawara, Reiki ; Kondo, Takeshi ; Yanada, Masamitsu ; Yamamoto, Kazuhito ; Kobayashi, Tsutomu ; Kuroda, Junya ; Usuki, Kensuke ; Utsu, Yoshikazu ; Aotsuka, Nobuyuki ; Yoshimitsu, Makoto ; Ishitsuka, Kenji ; Ono, Takaaki ; Takahashi, Naoto ; Iyama, Satoshi ; Nakamura, Makoto ; Nakamura, Yukinori ; Fukuhara, Suguru ; Izutsu, Koji ; Yamauchi, Nobuhiko ; Yuda, Junichiro ; Minami, Yosuke</creatorcontrib><description>Background: Recently, whole exome sequencing has been used for the next-generation sequencing of acute myeloid leukemia (AML), and certain gene mutations have been identified in patients with AML. The treatment strategies for leukemia have undergone drastic changes with the rapid development of new drugs. However, the proper use of newly developed agents poses a major challenge in AML treatment. Genome profiling analysis can be used to select the optimal treatment for patients with newly diagnosed AML.
Methods and Results: Hematologic malignancies (HM)-SCREEN-Japan 01 is an actionable mutation profiling multicenter study of patients with newly diagnosed AML who cannot be treated with first standard treatment or patients who have relapsed/refractory AML (R/R-AML). The objective of this study was to evaluate the frequency and characteristics of cancer-related genomic alterations in patients with AML using a comprehensive genome profiling assay (FoundationOne®Heme (F1H)) and determine the quality of specimens used in gene analysis. Before participant recruitment, approval was obtained from the institutional review board at each participating institution. The trial was registered in the UMIN Clinical Trials Registry (UMIN000035233).
This study was conducted at 17 participating institutions and had a sample size of 200. The eligibility criteria were as follows: 1) histological diagnosis of AML through bone marrow aspiration; 2) fulfillment of either of the following conditions: i) newly diagnosed AML unfit for standard treatment (ND-unfit AML) or ii) R/R-AML; 3) sufficient sample collection via bone marrow aspiration; 4) Age of participants 20 years or above during registration; 5) provision of written informed consent by participants. The primary outcome was the frequency of each genomic alteration, as determined using F1H, which is a comprehensive genome profiling test based on next-generation sequencing, in the AML specimens. The secondary outcome was the association between each genomic alteration and the clinicopathological characteristics, prognosis, and quality of specimens used in the genetic analysis. Serial genome profiling analyses were performed to evaluate the time-dependent changes in the genome profiles of patients administered FLT3 inhibitors, gilteritinib, and quizartinib for treating AML.
One hundred and eighty-two patients were recruited, and the F1H report was successfully obtained for 177 patients (97.3%). The median age of the 66 patients with ND-unfit AML was 73 years (63-79 years), and that of the 105 patients with R/R-AML was 50 years (41-68 years). The median turnaround time was 13 days (minimum 8 days). Recurrent alterations were observed in FLT3 (28.7%), TP53 (21.6%), RUNX1 (20.5%), DNMT3A (18.7%), NPM1 (18.7%), ASXL1 (15.2%), TET2 (14.0%), KMT2A-rearrangement (13.5%), and NRAS (13.5%). IDH1 and/or IDH2 mutations were identified in specimens collected from 30 patients (17.5%). Compared with the prevalence in 2247 patients with AML in the US and Europe who underwent F1H analysis, the frequencies of mutations in FLT3 (28.7% vs. 20.5%) and TP53 (21.6% vs. 17.0%) were higher in this Japanese cohort. Mutations in IDH2, PTPN11, and SF3B1 were observed along with KMT2A rearrangement. Mutations in TP53 tended to be exclusive to the FLT3 mutation. In comparison between the ND-unfit AML and R/R-AML, mutations in TET2 and ASXL1 tended to be more frequnt in ND-unfit AML (17.9% vs. 7.0%, p=0.038, 18.9% vs. 8.5%, p=0.055, respectively). The median expression level of WT1 mRNA at the time of sample collection was 4,490 copies/μgRNA (n=158), and WT1 mutation was frequently found in the WT1-high expression group (13.9% vs. 3.8%, p=0.03), suggesting that the mutation of WT1 may cause overexpression of WT1 as an oncogene.
Conclusions: In our evaluation of the suitability of F1H for HM-SCREEN-Japan 01, we successfully identified leukemia-associated genes that can be used as therapeutic targets in AML, which have rarely been identified thus far.
[Display omitted]
Yamauchi: Astellas: Research Funding; Abbie: Research Funding; Chugai: Honoraria; Pfizer: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria; Otsuka: Research Funding; Daiichi Sankyo: Research Funding; Solasia Pharma: Research Funding. Shibayama: Celgene: Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Avvie: Honoraria, Research Funding; Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Essentia Pharma Japan: Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Honoraria; Fujimoto: Honoraria; Nippon Shinyaku: Honoraria; Sanofi: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Otsuka: Honoraria; Mundi Pharma: Honoraria. Kondo: Astellas Pharma Inc.: Consultancy, Honoraria; Otsuka Pharmaceutical: Honoraria, Research Funding; Novartis Pharma KK: Honoraria; Bristol-Myers Squibb: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Sanwa Kagaku Kenkyusho: Consultancy. Yamamoto: Eisai: Honoraria, Research Funding; IQIVA/Incyte: Research Funding; IQIVA/HUYA: Honoraria; HUYA: Consultancy; Janssen: Honoraria; Kyowa Kirin: Honoraria; Meiji Seika Pharma: Consultancy, Honoraria, Research Funding; MSD: Honoraria; Mundipharma: Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Sanofi: Honoraria; Solasia Pharma: Research Funding; SymBio: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Yakult: Honoraria, Research Funding; Zenyaku: Honoraria, Research Funding; Micron: Honoraria; IQIVA/Genmab: Research Funding; ADC Therapeutics: Honoraria; Daiichi Sankyo: Honoraria; Chugai: Honoraria, Research Funding; Bristol-Myers Squibb/Celgene: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding. Kuroda: Sanofi: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Otsuka Pharmaceutical: Honoraria, Research Funding; Astellas Pharma: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; MSD: Research Funding; Abbvie: Consultancy, Honoraria; Ono Pharmaceutical: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Sysmex: Research Funding; Pfizer: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Shionogi: Research Funding; Asahi Kasei: Research Funding; Taiho Pharmaceutical: Research Funding; Fujimoto Pharmaceutical: Current Employment, Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Dainippon Sumitomo Pharma: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Bristol-MyersSquibb: Consultancy, Honoraria, Research Funding; Janssen Pharmaceutical K.K: Consultancy. Usuki: Nippon Boehringer Ingelheim: Research Funding; Takeda: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Janssen: Research Funding; Ono: Research Funding, Speakers Bureau; Brisol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Otsuka: Research Funding, Speakers Bureau; Sumitomo Dainippon: Research Funding; Daiichi Sankyo: Research Funding, Speakers Bureau; Symbio: Research Funding, Speakers Bureau; Gilead: Research Funding; Abbvie: Research Funding; Astellas: Research Funding, Speakers Bureau; Astellas-Amgen-Biopharma: Research Funding; Nippon shinyaku: Research Funding, Speakers Bureau; Kyowa Kirin: Research Funding, Speakers Bureau; Pfizer: Research Funding; Alexion: Speakers Bureau; Eisai: Speakers Bureau; MSD: Speakers Bureau; PharmaEssentia: Speakers Bureau; Yakult: Speakers Bureau; Mundipharma: Research Funding. Yoshimitsu: Sanofi: Honoraria; Takeda: Honoraria; Novartis: Honoraria. Ishitsuka: Eli Lilly: Research Funding; Mochida: Other: Personal fees, Research Funding; Eisai: Other: Personal fees, Research Funding; Sumitomo Dainippon Pharma: Other: Personal fees, Research Funding; Genzyme: Other: Personal fees; Astellas Pharma: Other: Personal fees, Research Funding; Pfizer: Other: Personal fees; Novartis: Other: Personal fees; Janssen Pharmaceuticals: Other: Personal fees; Taiho Pharmaceuticals: Other: Personal fees, Research Funding; Mundipharma: Other: Personal fees; Takeda: Other: Personal fees, Research Funding; BMS: Other; Chugai Pharmaceutical: Honoraria, Other: Personal fees, Research Funding; Celgene: Honoraria, Other: Personal fees; Ono Pharmaceutical: Other: Personal fees, Research Funding; Kyowa Kirin: Other: Personal fees, Research Funding; Daiichi Sankyo: Consultancy, Other: Personal fees; Shire: Other; Otsuka Pharmaceutical: Other: Personal fees; Teijin Pharma: Research Funding; MSD: Research Funding; Asahi kasei: Research Funding; Huya Japan: Other: Personal fees. Ono: DAIICHI SANKYO COMPANY, LIMITED.: Honoraria; Novartis Pharma KK: Honoraria; Bristol-Myers Squibb Company: Honoraria; Pfizer Japan Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria, Research Funding; Takeda Pharmaceutical Company Limited.: Honoraria; Astellas Pharma Inc.: Honoraria; Eisai Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K: Honoraria; Mundipharma K.K.: Honoraria; TAIHO PHARMACEUTICAL CO., LTD.: Research Funding; Kyowa Kirin Co., Ltd.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Merck Sharp & Dohme: Honoraria, Research Funding. Takahashi: Kyowahakko-Kirin: Research Funding; Ono: Research Funding; Asahikase</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2021-149960</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>Blood, 2021-11, Vol.138 (Supplement 1), p.4457-4457</ispartof><rights>2021 American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1850-d93f37e45edc1c473d8cba0dcceeb9165038ed9fb791c293fc7246f1ac76f68b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids></links><search><creatorcontrib>Hosono, Naoko</creatorcontrib><creatorcontrib>Yamauchi, Takahiro</creatorcontrib><creatorcontrib>Chi, SungGi</creatorcontrib><creatorcontrib>Fukushima, Kentaro</creatorcontrib><creatorcontrib>Shibayama, Hirohiko</creatorcontrib><creatorcontrib>Katagiri, Seiichiro</creatorcontrib><creatorcontrib>Gotoh, Akihiko</creatorcontrib><creatorcontrib>Eguchi, Motoki</creatorcontrib><creatorcontrib>Morishita, Takanobu</creatorcontrib><creatorcontrib>Ogasawara, Reiki</creatorcontrib><creatorcontrib>Kondo, Takeshi</creatorcontrib><creatorcontrib>Yanada, Masamitsu</creatorcontrib><creatorcontrib>Yamamoto, Kazuhito</creatorcontrib><creatorcontrib>Kobayashi, Tsutomu</creatorcontrib><creatorcontrib>Kuroda, Junya</creatorcontrib><creatorcontrib>Usuki, Kensuke</creatorcontrib><creatorcontrib>Utsu, Yoshikazu</creatorcontrib><creatorcontrib>Aotsuka, Nobuyuki</creatorcontrib><creatorcontrib>Yoshimitsu, Makoto</creatorcontrib><creatorcontrib>Ishitsuka, Kenji</creatorcontrib><creatorcontrib>Ono, Takaaki</creatorcontrib><creatorcontrib>Takahashi, Naoto</creatorcontrib><creatorcontrib>Iyama, Satoshi</creatorcontrib><creatorcontrib>Nakamura, Makoto</creatorcontrib><creatorcontrib>Nakamura, Yukinori</creatorcontrib><creatorcontrib>Fukuhara, Suguru</creatorcontrib><creatorcontrib>Izutsu, Koji</creatorcontrib><creatorcontrib>Yamauchi, Nobuhiko</creatorcontrib><creatorcontrib>Yuda, Junichiro</creatorcontrib><creatorcontrib>Minami, Yosuke</creatorcontrib><title>Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study on Patients with Acute Myeloid Leukemia</title><title>Blood</title><description>Background: Recently, whole exome sequencing has been used for the next-generation sequencing of acute myeloid leukemia (AML), and certain gene mutations have been identified in patients with AML. The treatment strategies for leukemia have undergone drastic changes with the rapid development of new drugs. However, the proper use of newly developed agents poses a major challenge in AML treatment. Genome profiling analysis can be used to select the optimal treatment for patients with newly diagnosed AML.
Methods and Results: Hematologic malignancies (HM)-SCREEN-Japan 01 is an actionable mutation profiling multicenter study of patients with newly diagnosed AML who cannot be treated with first standard treatment or patients who have relapsed/refractory AML (R/R-AML). The objective of this study was to evaluate the frequency and characteristics of cancer-related genomic alterations in patients with AML using a comprehensive genome profiling assay (FoundationOne®Heme (F1H)) and determine the quality of specimens used in gene analysis. Before participant recruitment, approval was obtained from the institutional review board at each participating institution. The trial was registered in the UMIN Clinical Trials Registry (UMIN000035233).
This study was conducted at 17 participating institutions and had a sample size of 200. The eligibility criteria were as follows: 1) histological diagnosis of AML through bone marrow aspiration; 2) fulfillment of either of the following conditions: i) newly diagnosed AML unfit for standard treatment (ND-unfit AML) or ii) R/R-AML; 3) sufficient sample collection via bone marrow aspiration; 4) Age of participants 20 years or above during registration; 5) provision of written informed consent by participants. The primary outcome was the frequency of each genomic alteration, as determined using F1H, which is a comprehensive genome profiling test based on next-generation sequencing, in the AML specimens. The secondary outcome was the association between each genomic alteration and the clinicopathological characteristics, prognosis, and quality of specimens used in the genetic analysis. Serial genome profiling analyses were performed to evaluate the time-dependent changes in the genome profiles of patients administered FLT3 inhibitors, gilteritinib, and quizartinib for treating AML.
One hundred and eighty-two patients were recruited, and the F1H report was successfully obtained for 177 patients (97.3%). The median age of the 66 patients with ND-unfit AML was 73 years (63-79 years), and that of the 105 patients with R/R-AML was 50 years (41-68 years). The median turnaround time was 13 days (minimum 8 days). Recurrent alterations were observed in FLT3 (28.7%), TP53 (21.6%), RUNX1 (20.5%), DNMT3A (18.7%), NPM1 (18.7%), ASXL1 (15.2%), TET2 (14.0%), KMT2A-rearrangement (13.5%), and NRAS (13.5%). IDH1 and/or IDH2 mutations were identified in specimens collected from 30 patients (17.5%). Compared with the prevalence in 2247 patients with AML in the US and Europe who underwent F1H analysis, the frequencies of mutations in FLT3 (28.7% vs. 20.5%) and TP53 (21.6% vs. 17.0%) were higher in this Japanese cohort. Mutations in IDH2, PTPN11, and SF3B1 were observed along with KMT2A rearrangement. Mutations in TP53 tended to be exclusive to the FLT3 mutation. In comparison between the ND-unfit AML and R/R-AML, mutations in TET2 and ASXL1 tended to be more frequnt in ND-unfit AML (17.9% vs. 7.0%, p=0.038, 18.9% vs. 8.5%, p=0.055, respectively). The median expression level of WT1 mRNA at the time of sample collection was 4,490 copies/μgRNA (n=158), and WT1 mutation was frequently found in the WT1-high expression group (13.9% vs. 3.8%, p=0.03), suggesting that the mutation of WT1 may cause overexpression of WT1 as an oncogene.
Conclusions: In our evaluation of the suitability of F1H for HM-SCREEN-Japan 01, we successfully identified leukemia-associated genes that can be used as therapeutic targets in AML, which have rarely been identified thus far.
[Display omitted]
Yamauchi: Astellas: Research Funding; Abbie: Research Funding; Chugai: Honoraria; Pfizer: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria; Otsuka: Research Funding; Daiichi Sankyo: Research Funding; Solasia Pharma: Research Funding. Shibayama: Celgene: Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Avvie: Honoraria, Research Funding; Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Essentia Pharma Japan: Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Honoraria; Fujimoto: Honoraria; Nippon Shinyaku: Honoraria; Sanofi: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Otsuka: Honoraria; Mundi Pharma: Honoraria. Kondo: Astellas Pharma Inc.: Consultancy, Honoraria; Otsuka Pharmaceutical: Honoraria, Research Funding; Novartis Pharma KK: Honoraria; Bristol-Myers Squibb: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Sanwa Kagaku Kenkyusho: Consultancy. Yamamoto: Eisai: Honoraria, Research Funding; IQIVA/Incyte: Research Funding; IQIVA/HUYA: Honoraria; HUYA: Consultancy; Janssen: Honoraria; Kyowa Kirin: Honoraria; Meiji Seika Pharma: Consultancy, Honoraria, Research Funding; MSD: Honoraria; Mundipharma: Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Sanofi: Honoraria; Solasia Pharma: Research Funding; SymBio: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Yakult: Honoraria, Research Funding; Zenyaku: Honoraria, Research Funding; Micron: Honoraria; IQIVA/Genmab: Research Funding; ADC Therapeutics: Honoraria; Daiichi Sankyo: Honoraria; Chugai: Honoraria, Research Funding; Bristol-Myers Squibb/Celgene: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding. Kuroda: Sanofi: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Otsuka Pharmaceutical: Honoraria, Research Funding; Astellas Pharma: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; MSD: Research Funding; Abbvie: Consultancy, Honoraria; Ono Pharmaceutical: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Sysmex: Research Funding; Pfizer: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Shionogi: Research Funding; Asahi Kasei: Research Funding; Taiho Pharmaceutical: Research Funding; Fujimoto Pharmaceutical: Current Employment, Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Dainippon Sumitomo Pharma: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Bristol-MyersSquibb: Consultancy, Honoraria, Research Funding; Janssen Pharmaceutical K.K: Consultancy. Usuki: Nippon Boehringer Ingelheim: Research Funding; Takeda: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Janssen: Research Funding; Ono: Research Funding, Speakers Bureau; Brisol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Otsuka: Research Funding, Speakers Bureau; Sumitomo Dainippon: Research Funding; Daiichi Sankyo: Research Funding, Speakers Bureau; Symbio: Research Funding, Speakers Bureau; Gilead: Research Funding; Abbvie: Research Funding; Astellas: Research Funding, Speakers Bureau; Astellas-Amgen-Biopharma: Research Funding; Nippon shinyaku: Research Funding, Speakers Bureau; Kyowa Kirin: Research Funding, Speakers Bureau; Pfizer: Research Funding; Alexion: Speakers Bureau; Eisai: Speakers Bureau; MSD: Speakers Bureau; PharmaEssentia: Speakers Bureau; Yakult: Speakers Bureau; Mundipharma: Research Funding. Yoshimitsu: Sanofi: Honoraria; Takeda: Honoraria; Novartis: Honoraria. Ishitsuka: Eli Lilly: Research Funding; Mochida: Other: Personal fees, Research Funding; Eisai: Other: Personal fees, Research Funding; Sumitomo Dainippon Pharma: Other: Personal fees, Research Funding; Genzyme: Other: Personal fees; Astellas Pharma: Other: Personal fees, Research Funding; Pfizer: Other: Personal fees; Novartis: Other: Personal fees; Janssen Pharmaceuticals: Other: Personal fees; Taiho Pharmaceuticals: Other: Personal fees, Research Funding; Mundipharma: Other: Personal fees; Takeda: Other: Personal fees, Research Funding; BMS: Other; Chugai Pharmaceutical: Honoraria, Other: Personal fees, Research Funding; Celgene: Honoraria, Other: Personal fees; Ono Pharmaceutical: Other: Personal fees, Research Funding; Kyowa Kirin: Other: Personal fees, Research Funding; Daiichi Sankyo: Consultancy, Other: Personal fees; Shire: Other; Otsuka Pharmaceutical: Other: Personal fees; Teijin Pharma: Research Funding; MSD: Research Funding; Asahi kasei: Research Funding; Huya Japan: Other: Personal fees. Ono: DAIICHI SANKYO COMPANY, LIMITED.: Honoraria; Novartis Pharma KK: Honoraria; Bristol-Myers Squibb Company: Honoraria; Pfizer Japan Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria, Research Funding; Takeda Pharmaceutical Company Limited.: Honoraria; Astellas Pharma Inc.: Honoraria; Eisai Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K: Honoraria; Mundipharma K.K.: Honoraria; TAIHO PHARMACEUTICAL CO., LTD.: Research Funding; Kyowa Kirin Co., Ltd.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Merck Sharp & Dohme: Honoraria, Research Funding. Takahashi: Kyowahakko-Kirin: Research Funding; Ono: Research Funding; Asahikase</description><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEQhoMoWKs_wFuOeogm2W89FVGrtChUzyE7ma3RbVKyWaUH_7tb69nTwDvvMwwPIaeCXwhRysu69d4wyaVgIq2qnO-RkchkyTiXfJ-MOOc5S6tCHJKjrnvnXKSJzEbke4orHX3rlxboXLd26bQDix09m87P2QIComOPeq0d5eKKTui8jzpa7-hz8I1trVsOURstoIsY6CL2ZkO366E1RB39svGNTqCPSOcbbL01dIb9B66sPiYHjW47PPmbY_J6d_tyM2Wzp_uHm8mMgSgzzkyVNEmBaYYGBKRFYkqoNTcAiHUl8ownJZqqqYtKgBzKUMg0b4SGIm_ysk7GROzuQvBdF7BR62BXOmyU4GrrT_36U1t_audvYK53DA6PfVoMqhu8OEBjA0JUxtt_6B-Z1Hn7</recordid><startdate>20211123</startdate><enddate>20211123</enddate><creator>Hosono, Naoko</creator><creator>Yamauchi, Takahiro</creator><creator>Chi, SungGi</creator><creator>Fukushima, Kentaro</creator><creator>Shibayama, Hirohiko</creator><creator>Katagiri, Seiichiro</creator><creator>Gotoh, Akihiko</creator><creator>Eguchi, Motoki</creator><creator>Morishita, Takanobu</creator><creator>Ogasawara, Reiki</creator><creator>Kondo, Takeshi</creator><creator>Yanada, Masamitsu</creator><creator>Yamamoto, Kazuhito</creator><creator>Kobayashi, Tsutomu</creator><creator>Kuroda, Junya</creator><creator>Usuki, Kensuke</creator><creator>Utsu, Yoshikazu</creator><creator>Aotsuka, Nobuyuki</creator><creator>Yoshimitsu, Makoto</creator><creator>Ishitsuka, Kenji</creator><creator>Ono, Takaaki</creator><creator>Takahashi, Naoto</creator><creator>Iyama, Satoshi</creator><creator>Nakamura, Makoto</creator><creator>Nakamura, Yukinori</creator><creator>Fukuhara, Suguru</creator><creator>Izutsu, Koji</creator><creator>Yamauchi, Nobuhiko</creator><creator>Yuda, Junichiro</creator><creator>Minami, Yosuke</creator><general>Elsevier Inc</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20211123</creationdate><title>Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study on Patients with Acute Myeloid Leukemia</title><author>Hosono, Naoko ; Yamauchi, Takahiro ; Chi, SungGi ; Fukushima, Kentaro ; Shibayama, Hirohiko ; Katagiri, Seiichiro ; Gotoh, Akihiko ; Eguchi, Motoki ; Morishita, Takanobu ; Ogasawara, Reiki ; Kondo, Takeshi ; Yanada, Masamitsu ; Yamamoto, Kazuhito ; Kobayashi, Tsutomu ; Kuroda, Junya ; Usuki, Kensuke ; Utsu, Yoshikazu ; Aotsuka, Nobuyuki ; Yoshimitsu, Makoto ; Ishitsuka, Kenji ; Ono, Takaaki ; Takahashi, Naoto ; Iyama, Satoshi ; Nakamura, Makoto ; Nakamura, Yukinori ; Fukuhara, Suguru ; Izutsu, Koji ; Yamauchi, Nobuhiko ; Yuda, Junichiro ; Minami, Yosuke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1850-d93f37e45edc1c473d8cba0dcceeb9165038ed9fb791c293fc7246f1ac76f68b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hosono, Naoko</creatorcontrib><creatorcontrib>Yamauchi, Takahiro</creatorcontrib><creatorcontrib>Chi, SungGi</creatorcontrib><creatorcontrib>Fukushima, Kentaro</creatorcontrib><creatorcontrib>Shibayama, Hirohiko</creatorcontrib><creatorcontrib>Katagiri, Seiichiro</creatorcontrib><creatorcontrib>Gotoh, Akihiko</creatorcontrib><creatorcontrib>Eguchi, Motoki</creatorcontrib><creatorcontrib>Morishita, Takanobu</creatorcontrib><creatorcontrib>Ogasawara, Reiki</creatorcontrib><creatorcontrib>Kondo, Takeshi</creatorcontrib><creatorcontrib>Yanada, Masamitsu</creatorcontrib><creatorcontrib>Yamamoto, Kazuhito</creatorcontrib><creatorcontrib>Kobayashi, Tsutomu</creatorcontrib><creatorcontrib>Kuroda, Junya</creatorcontrib><creatorcontrib>Usuki, Kensuke</creatorcontrib><creatorcontrib>Utsu, Yoshikazu</creatorcontrib><creatorcontrib>Aotsuka, Nobuyuki</creatorcontrib><creatorcontrib>Yoshimitsu, Makoto</creatorcontrib><creatorcontrib>Ishitsuka, Kenji</creatorcontrib><creatorcontrib>Ono, Takaaki</creatorcontrib><creatorcontrib>Takahashi, Naoto</creatorcontrib><creatorcontrib>Iyama, Satoshi</creatorcontrib><creatorcontrib>Nakamura, Makoto</creatorcontrib><creatorcontrib>Nakamura, Yukinori</creatorcontrib><creatorcontrib>Fukuhara, Suguru</creatorcontrib><creatorcontrib>Izutsu, Koji</creatorcontrib><creatorcontrib>Yamauchi, Nobuhiko</creatorcontrib><creatorcontrib>Yuda, Junichiro</creatorcontrib><creatorcontrib>Minami, Yosuke</creatorcontrib><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hosono, Naoko</au><au>Yamauchi, Takahiro</au><au>Chi, SungGi</au><au>Fukushima, Kentaro</au><au>Shibayama, Hirohiko</au><au>Katagiri, Seiichiro</au><au>Gotoh, Akihiko</au><au>Eguchi, Motoki</au><au>Morishita, Takanobu</au><au>Ogasawara, Reiki</au><au>Kondo, Takeshi</au><au>Yanada, Masamitsu</au><au>Yamamoto, Kazuhito</au><au>Kobayashi, Tsutomu</au><au>Kuroda, Junya</au><au>Usuki, Kensuke</au><au>Utsu, Yoshikazu</au><au>Aotsuka, Nobuyuki</au><au>Yoshimitsu, Makoto</au><au>Ishitsuka, Kenji</au><au>Ono, Takaaki</au><au>Takahashi, Naoto</au><au>Iyama, Satoshi</au><au>Nakamura, Makoto</au><au>Nakamura, Yukinori</au><au>Fukuhara, Suguru</au><au>Izutsu, Koji</au><au>Yamauchi, Nobuhiko</au><au>Yuda, Junichiro</au><au>Minami, Yosuke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study on Patients with Acute Myeloid Leukemia</atitle><jtitle>Blood</jtitle><date>2021-11-23</date><risdate>2021</risdate><volume>138</volume><issue>Supplement 1</issue><spage>4457</spage><epage>4457</epage><pages>4457-4457</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Background: Recently, whole exome sequencing has been used for the next-generation sequencing of acute myeloid leukemia (AML), and certain gene mutations have been identified in patients with AML. The treatment strategies for leukemia have undergone drastic changes with the rapid development of new drugs. However, the proper use of newly developed agents poses a major challenge in AML treatment. Genome profiling analysis can be used to select the optimal treatment for patients with newly diagnosed AML.
Methods and Results: Hematologic malignancies (HM)-SCREEN-Japan 01 is an actionable mutation profiling multicenter study of patients with newly diagnosed AML who cannot be treated with first standard treatment or patients who have relapsed/refractory AML (R/R-AML). The objective of this study was to evaluate the frequency and characteristics of cancer-related genomic alterations in patients with AML using a comprehensive genome profiling assay (FoundationOne®Heme (F1H)) and determine the quality of specimens used in gene analysis. Before participant recruitment, approval was obtained from the institutional review board at each participating institution. The trial was registered in the UMIN Clinical Trials Registry (UMIN000035233).
This study was conducted at 17 participating institutions and had a sample size of 200. The eligibility criteria were as follows: 1) histological diagnosis of AML through bone marrow aspiration; 2) fulfillment of either of the following conditions: i) newly diagnosed AML unfit for standard treatment (ND-unfit AML) or ii) R/R-AML; 3) sufficient sample collection via bone marrow aspiration; 4) Age of participants 20 years or above during registration; 5) provision of written informed consent by participants. The primary outcome was the frequency of each genomic alteration, as determined using F1H, which is a comprehensive genome profiling test based on next-generation sequencing, in the AML specimens. The secondary outcome was the association between each genomic alteration and the clinicopathological characteristics, prognosis, and quality of specimens used in the genetic analysis. Serial genome profiling analyses were performed to evaluate the time-dependent changes in the genome profiles of patients administered FLT3 inhibitors, gilteritinib, and quizartinib for treating AML.
One hundred and eighty-two patients were recruited, and the F1H report was successfully obtained for 177 patients (97.3%). The median age of the 66 patients with ND-unfit AML was 73 years (63-79 years), and that of the 105 patients with R/R-AML was 50 years (41-68 years). The median turnaround time was 13 days (minimum 8 days). Recurrent alterations were observed in FLT3 (28.7%), TP53 (21.6%), RUNX1 (20.5%), DNMT3A (18.7%), NPM1 (18.7%), ASXL1 (15.2%), TET2 (14.0%), KMT2A-rearrangement (13.5%), and NRAS (13.5%). IDH1 and/or IDH2 mutations were identified in specimens collected from 30 patients (17.5%). Compared with the prevalence in 2247 patients with AML in the US and Europe who underwent F1H analysis, the frequencies of mutations in FLT3 (28.7% vs. 20.5%) and TP53 (21.6% vs. 17.0%) were higher in this Japanese cohort. Mutations in IDH2, PTPN11, and SF3B1 were observed along with KMT2A rearrangement. Mutations in TP53 tended to be exclusive to the FLT3 mutation. In comparison between the ND-unfit AML and R/R-AML, mutations in TET2 and ASXL1 tended to be more frequnt in ND-unfit AML (17.9% vs. 7.0%, p=0.038, 18.9% vs. 8.5%, p=0.055, respectively). The median expression level of WT1 mRNA at the time of sample collection was 4,490 copies/μgRNA (n=158), and WT1 mutation was frequently found in the WT1-high expression group (13.9% vs. 3.8%, p=0.03), suggesting that the mutation of WT1 may cause overexpression of WT1 as an oncogene.
Conclusions: In our evaluation of the suitability of F1H for HM-SCREEN-Japan 01, we successfully identified leukemia-associated genes that can be used as therapeutic targets in AML, which have rarely been identified thus far.
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Yamauchi: Astellas: Research Funding; Abbie: Research Funding; Chugai: Honoraria; Pfizer: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria; Otsuka: Research Funding; Daiichi Sankyo: Research Funding; Solasia Pharma: Research Funding. Shibayama: Celgene: Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Avvie: Honoraria, Research Funding; Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Essentia Pharma Japan: Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Honoraria; Fujimoto: Honoraria; Nippon Shinyaku: Honoraria; Sanofi: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Otsuka: Honoraria; Mundi Pharma: Honoraria. Kondo: Astellas Pharma Inc.: Consultancy, Honoraria; Otsuka Pharmaceutical: Honoraria, Research Funding; Novartis Pharma KK: Honoraria; Bristol-Myers Squibb: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Sanwa Kagaku Kenkyusho: Consultancy. Yamamoto: Eisai: Honoraria, Research Funding; IQIVA/Incyte: Research Funding; IQIVA/HUYA: Honoraria; HUYA: Consultancy; Janssen: Honoraria; Kyowa Kirin: Honoraria; Meiji Seika Pharma: Consultancy, Honoraria, Research Funding; MSD: Honoraria; Mundipharma: Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Sanofi: Honoraria; Solasia Pharma: Research Funding; SymBio: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Yakult: Honoraria, Research Funding; Zenyaku: Honoraria, Research Funding; Micron: Honoraria; IQIVA/Genmab: Research Funding; ADC Therapeutics: Honoraria; Daiichi Sankyo: Honoraria; Chugai: Honoraria, Research Funding; Bristol-Myers Squibb/Celgene: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding. Kuroda: Sanofi: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Otsuka Pharmaceutical: Honoraria, Research Funding; Astellas Pharma: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; MSD: Research Funding; Abbvie: Consultancy, Honoraria; Ono Pharmaceutical: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Sysmex: Research Funding; Pfizer: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Shionogi: Research Funding; Asahi Kasei: Research Funding; Taiho Pharmaceutical: Research Funding; Fujimoto Pharmaceutical: Current Employment, Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Dainippon Sumitomo Pharma: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Bristol-MyersSquibb: Consultancy, Honoraria, Research Funding; Janssen Pharmaceutical K.K: Consultancy. Usuki: Nippon Boehringer Ingelheim: Research Funding; Takeda: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Janssen: Research Funding; Ono: Research Funding, Speakers Bureau; Brisol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Otsuka: Research Funding, Speakers Bureau; Sumitomo Dainippon: Research Funding; Daiichi Sankyo: Research Funding, Speakers Bureau; Symbio: Research Funding, Speakers Bureau; Gilead: Research Funding; Abbvie: Research Funding; Astellas: Research Funding, Speakers Bureau; Astellas-Amgen-Biopharma: Research Funding; Nippon shinyaku: Research Funding, Speakers Bureau; Kyowa Kirin: Research Funding, Speakers Bureau; Pfizer: Research Funding; Alexion: Speakers Bureau; Eisai: Speakers Bureau; MSD: Speakers Bureau; PharmaEssentia: Speakers Bureau; Yakult: Speakers Bureau; Mundipharma: Research Funding. Yoshimitsu: Sanofi: Honoraria; Takeda: Honoraria; Novartis: Honoraria. Ishitsuka: Eli Lilly: Research Funding; Mochida: Other: Personal fees, Research Funding; Eisai: Other: Personal fees, Research Funding; Sumitomo Dainippon Pharma: Other: Personal fees, Research Funding; Genzyme: Other: Personal fees; Astellas Pharma: Other: Personal fees, Research Funding; Pfizer: Other: Personal fees; Novartis: Other: Personal fees; Janssen Pharmaceuticals: Other: Personal fees; Taiho Pharmaceuticals: Other: Personal fees, Research Funding; Mundipharma: Other: Personal fees; Takeda: Other: Personal fees, Research Funding; BMS: Other; Chugai Pharmaceutical: Honoraria, Other: Personal fees, Research Funding; Celgene: Honoraria, Other: Personal fees; Ono Pharmaceutical: Other: Personal fees, Research Funding; Kyowa Kirin: Other: Personal fees, Research Funding; Daiichi Sankyo: Consultancy, Other: Personal fees; Shire: Other; Otsuka Pharmaceutical: Other: Personal fees; Teijin Pharma: Research Funding; MSD: Research Funding; Asahi kasei: Research Funding; Huya Japan: Other: Personal fees. Ono: DAIICHI SANKYO COMPANY, LIMITED.: Honoraria; Novartis Pharma KK: Honoraria; Bristol-Myers Squibb Company: Honoraria; Pfizer Japan Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria, Research Funding; Takeda Pharmaceutical Company Limited.: Honoraria; Astellas Pharma Inc.: Honoraria; Eisai Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K: Honoraria; Mundipharma K.K.: Honoraria; TAIHO PHARMACEUTICAL CO., LTD.: Research Funding; Kyowa Kirin Co., Ltd.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Merck Sharp & Dohme: Honoraria, Research Funding. Takahashi: Kyowahakko-Kirin: Research Funding; Ono: Research Funding; Asahikase</abstract><pub>Elsevier Inc</pub><doi>10.1182/blood-2021-149960</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| title | Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study on Patients with Acute Myeloid Leukemia |
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