Pub Date : 2024-07-10DOI: 10.1038/s41375-024-02341-4
Fabio Efficace, Francois-Xavier Mahon, Johan Richter, Alfonso Piciocchi, Marta Cipriani, Franck E. Nicolini, Jiri Mayer, Daniela Zackova, Jeroen J. W. M. Janssen, Panayiotis Panayiotidis, Hanne Vestergaard, Perttu Koskenvesa, Antonio Almeida, Henrik Hjorth-Hansen, Joaquin Martinez-Lopez, Ulla Olsson-Strömberg, Andreas Hochhaus, Marc G. Berger, Gabriel Etienne, Hana Klamova, Edgar Faber, Philippe Rousselot, Markus Pfirrmann, Susanne Saussele
Limited data is available on the health-related quality of life (HRQoL) and symptoms of patients with chronic myeloid leukemia (CML) who are in treatment-free remission (TFR). We herein report HRQoL results from the EURO-SKI trial. Patients who had been on tyrosine kinase inhibitors (TKIs) therapy for at least 3 years and achieved MR4 for at least 1 year were enrolled from 11 European countries, and the EORTC QLQ-C30 and the FACIT-Fatigue questionnaires were used to assess HRQoL and fatigue respectively. Patients were categorized into the following age groups: 18–39, 40–59, 60–69 and ≥70 years. Of 728 patients evaluated at baseline, 686 (94%) completed HRQoL assessments. The median age at TKI discontinuation was 60 years. Our findings indicate that HRQoL and symptom trajectories may vary depending on specific age groups, with younger patients benefiting the most. Improvements in patients aged 60 years or older were marginal across several HRQoL and symptom domains. At the time of considering TKI discontinuation, physicians could inform younger patients that they may expect valuable HRQoL benefits. Considering the marginal improvements observed in patients aged 60 years or above, it may be important to further investigate the value of TFR compared to a lowest effective dose approach in this older group of patients.
{"title":"Health-related quality of life and symptoms of chronic myeloid leukemia patients after discontinuation of tyrosine kinase inhibitors: results from the EURO-SKI Trial","authors":"Fabio Efficace, Francois-Xavier Mahon, Johan Richter, Alfonso Piciocchi, Marta Cipriani, Franck E. Nicolini, Jiri Mayer, Daniela Zackova, Jeroen J. W. M. Janssen, Panayiotis Panayiotidis, Hanne Vestergaard, Perttu Koskenvesa, Antonio Almeida, Henrik Hjorth-Hansen, Joaquin Martinez-Lopez, Ulla Olsson-Strömberg, Andreas Hochhaus, Marc G. Berger, Gabriel Etienne, Hana Klamova, Edgar Faber, Philippe Rousselot, Markus Pfirrmann, Susanne Saussele","doi":"10.1038/s41375-024-02341-4","DOIUrl":"10.1038/s41375-024-02341-4","url":null,"abstract":"Limited data is available on the health-related quality of life (HRQoL) and symptoms of patients with chronic myeloid leukemia (CML) who are in treatment-free remission (TFR). We herein report HRQoL results from the EURO-SKI trial. Patients who had been on tyrosine kinase inhibitors (TKIs) therapy for at least 3 years and achieved MR4 for at least 1 year were enrolled from 11 European countries, and the EORTC QLQ-C30 and the FACIT-Fatigue questionnaires were used to assess HRQoL and fatigue respectively. Patients were categorized into the following age groups: 18–39, 40–59, 60–69 and ≥70 years. Of 728 patients evaluated at baseline, 686 (94%) completed HRQoL assessments. The median age at TKI discontinuation was 60 years. Our findings indicate that HRQoL and symptom trajectories may vary depending on specific age groups, with younger patients benefiting the most. Improvements in patients aged 60 years or older were marginal across several HRQoL and symptom domains. At the time of considering TKI discontinuation, physicians could inform younger patients that they may expect valuable HRQoL benefits. Considering the marginal improvements observed in patients aged 60 years or above, it may be important to further investigate the value of TFR compared to a lowest effective dose approach in this older group of patients.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02341-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1038/s41375-024-02330-7
Steffen Koschmieder, Prithviraj Bose, Martin H. Ellis, Vikas Gupta, Jean-Jacques Kiladjian, John Mascarenhas, Vikram Mathews, Francesco Passamonti, Claire Harrison
{"title":"Myelofibrosis management in routine clinical practice with a focus on patients with cytopenias: recommendations from a global consensus group","authors":"Steffen Koschmieder, Prithviraj Bose, Martin H. Ellis, Vikas Gupta, Jean-Jacques Kiladjian, John Mascarenhas, Vikram Mathews, Francesco Passamonti, Claire Harrison","doi":"10.1038/s41375-024-02330-7","DOIUrl":"10.1038/s41375-024-02330-7","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1038/s41375-024-02323-6
Olisaemeka Ogbue, Tariq Kewan, Carlos Bravo-Perez, Serhan Unlu, Naomi Kawashima, Nakisha D. Williams, Arooj Ahmed, Luca Guarnera, Carmelo Gurnari, Valeria Visconte, Jaroslaw P. Maciejewski
{"title":"Hemolytic versus malproductive anemia in large granular lymphocytic leukemia","authors":"Olisaemeka Ogbue, Tariq Kewan, Carlos Bravo-Perez, Serhan Unlu, Naomi Kawashima, Nakisha D. Williams, Arooj Ahmed, Luca Guarnera, Carmelo Gurnari, Valeria Visconte, Jaroslaw P. Maciejewski","doi":"10.1038/s41375-024-02323-6","DOIUrl":"10.1038/s41375-024-02323-6","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1038/s41375-024-02331-6
Hyoju Kim, Tze King Tan, Dean Zi Yang Lee, Xiao Zi Huang, Jolynn Zu Lin Ong, Michelle A. Kelliher, Allen Eng Juh Yeoh, Takaomi Sanda, Shi Hao Tan
T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy arising from immature thymocytes. Unlike well-known oncogenic transcription factors, such as NOTCH1 and MYC, the involvement of chromatin remodeling factors in T-ALL pathogenesis is poorly understood. Here, we provide compelling evidence on how SWI/SNF chromatin remodeling complex contributes to human T-ALL pathogenesis. Integrative analysis of transcriptomic and ATAC-Seq datasets revealed high expression of SMARCA4, one of the subunits of the SWI/SNF complex, in T-ALL patient samples and cell lines compared to normal T cells. Loss of SMARCA protein function resulted in apoptosis induction and growth inhibition in multiple T-ALL cell lines. ATAC-Seq analysis revealed a massive reduction in chromatin accessibility across the genome after the loss of SMARCA protein function. RUNX1 interacts with SMARCA4 protein and co-occupies the same genomic regions. Importantly, the NOTCH1-MYC pathway was primarily affected when SMARCA protein function was impaired, implicating SWI/SNF as a novel therapeutic target.
{"title":"Oncogenic dependency on SWI/SNF chromatin remodeling factors in T-cell acute lymphoblastic leukemia","authors":"Hyoju Kim, Tze King Tan, Dean Zi Yang Lee, Xiao Zi Huang, Jolynn Zu Lin Ong, Michelle A. Kelliher, Allen Eng Juh Yeoh, Takaomi Sanda, Shi Hao Tan","doi":"10.1038/s41375-024-02331-6","DOIUrl":"10.1038/s41375-024-02331-6","url":null,"abstract":"T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy arising from immature thymocytes. Unlike well-known oncogenic transcription factors, such as NOTCH1 and MYC, the involvement of chromatin remodeling factors in T-ALL pathogenesis is poorly understood. Here, we provide compelling evidence on how SWI/SNF chromatin remodeling complex contributes to human T-ALL pathogenesis. Integrative analysis of transcriptomic and ATAC-Seq datasets revealed high expression of SMARCA4, one of the subunits of the SWI/SNF complex, in T-ALL patient samples and cell lines compared to normal T cells. Loss of SMARCA protein function resulted in apoptosis induction and growth inhibition in multiple T-ALL cell lines. ATAC-Seq analysis revealed a massive reduction in chromatin accessibility across the genome after the loss of SMARCA protein function. RUNX1 interacts with SMARCA4 protein and co-occupies the same genomic regions. Importantly, the NOTCH1-MYC pathway was primarily affected when SMARCA protein function was impaired, implicating SWI/SNF as a novel therapeutic target.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02331-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1038/s41375-024-02298-4
Ibrahim N. Muhsen, Abba C. Zubair, Tobias Niederwieser, Shahrukh K. Hashmi
{"title":"Space exploration and cancer: the risks of deeper space adventures","authors":"Ibrahim N. Muhsen, Abba C. Zubair, Tobias Niederwieser, Shahrukh K. Hashmi","doi":"10.1038/s41375-024-02298-4","DOIUrl":"10.1038/s41375-024-02298-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1038/s41375-024-02329-0
Anthony V. Moorman, Amir Enshaei, Daniel Murdy, Melvin Joy, Judith M. Boer, Monique L. den Boer, Rob Pieters, Valerie de Haas, Martin A. Horstmann, Gabriele Escherich, Bertil Johansson, Hanne V. Marquart, Kjeld Schmiegelow, Jeremy Hancock, John Moppett, Mats Heyman
{"title":"Integration of genetics and MRD to define low risk patients with B-cell precursor acute lymphoblastic leukaemia with intermediate MRD levels at the end of induction","authors":"Anthony V. Moorman, Amir Enshaei, Daniel Murdy, Melvin Joy, Judith M. Boer, Monique L. den Boer, Rob Pieters, Valerie de Haas, Martin A. Horstmann, Gabriele Escherich, Bertil Johansson, Hanne V. Marquart, Kjeld Schmiegelow, Jeremy Hancock, John Moppett, Mats Heyman","doi":"10.1038/s41375-024-02329-0","DOIUrl":"10.1038/s41375-024-02329-0","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02329-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1038/s41375-024-02327-2
Philipp Ernst, Jenny Rinke, Georg-Nikolaus Franke, Frank Dicker, Torsten Haferlach, Thomas Ernst, Andreas Hochhaus
{"title":"Treatment-free remission after third-line therapy with asciminib in chronic myeloid leukemia with an atypical e19a2 BCR::ABL1 transcript and T315I mutation","authors":"Philipp Ernst, Jenny Rinke, Georg-Nikolaus Franke, Frank Dicker, Torsten Haferlach, Thomas Ernst, Andreas Hochhaus","doi":"10.1038/s41375-024-02327-2","DOIUrl":"10.1038/s41375-024-02327-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02327-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1038/s41375-024-02333-4
Alberto Hernández-Sánchez, Teresa González, Marta Sobas, Eric Sträng, Gastone Castellani, María Abáigar, Peter J. M. Valk, Ángela Villaverde Ramiro, Axel Benner, Klaus H. Metzeler, Raúl Azibeiro, Jesse M. Tettero, Joaquín Martínez-López, Marta Pratcorona, Javier Martínez Elicegui, Ken I. Mills, Christian Thiede, Guillermo Sanz, Konstanze Döhner, Michael Heuser, Torsten Haferlach, Amin T. Turki, Dirk Reinhardt, Renate Schulze-Rath, Martje Barbus, Jesús María Hernández-Rivas, Brian Huntly, Gert Ossenkoppele, Hartmut Döhner, Lars Bullinger
Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.
{"title":"Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications – a HARMONY study","authors":"Alberto Hernández-Sánchez, Teresa González, Marta Sobas, Eric Sträng, Gastone Castellani, María Abáigar, Peter J. M. Valk, Ángela Villaverde Ramiro, Axel Benner, Klaus H. Metzeler, Raúl Azibeiro, Jesse M. Tettero, Joaquín Martínez-López, Marta Pratcorona, Javier Martínez Elicegui, Ken I. Mills, Christian Thiede, Guillermo Sanz, Konstanze Döhner, Michael Heuser, Torsten Haferlach, Amin T. Turki, Dirk Reinhardt, Renate Schulze-Rath, Martje Barbus, Jesús María Hernández-Rivas, Brian Huntly, Gert Ossenkoppele, Hartmut Döhner, Lars Bullinger","doi":"10.1038/s41375-024-02333-4","DOIUrl":"10.1038/s41375-024-02333-4","url":null,"abstract":"Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02333-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.1038/s41375-024-02291-x
Jonathan D. Diedrich, Qian Dong, Daniel C. Ferguson, Brennan P. Bergeron, Robert J. Autry, Maoxiang Qian, Wenjian Yang, Colton Smith, James B. Papizan, Jon P. Connelly, Kohei Hagiwara, Kristine R. Crews, Shondra M. Pruett-Miller, Ching-Hon Pui, Jun J. Yang, Mary V. Relling, William E. Evans, Daniel Savic
{"title":"Correction: Profiling chromatin accessibility in pediatric acute lymphoblastic leukemia identifies subtype-specific chromatin landscapes and gene regulatory networks","authors":"Jonathan D. Diedrich, Qian Dong, Daniel C. Ferguson, Brennan P. Bergeron, Robert J. Autry, Maoxiang Qian, Wenjian Yang, Colton Smith, James B. Papizan, Jon P. Connelly, Kohei Hagiwara, Kristine R. Crews, Shondra M. Pruett-Miller, Ching-Hon Pui, Jun J. Yang, Mary V. Relling, William E. Evans, Daniel Savic","doi":"10.1038/s41375-024-02291-x","DOIUrl":"10.1038/s41375-024-02291-x","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02291-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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