Venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation

Background: Chronic myelomonocytic leukemia is a clonal hematological disorder with an inherent risk of transformation to acute myeloid leukemia. Recently, there has been exponential discovery of molecular abnormalities in patients with chronic myelomonocytic leukemia. Some of these mutations indepe...

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Main Authors: Emiko Kashima, Yuka Sugimoto, Keiki Nagaharu, Eiko Ohya, Makoto Ikejiri, Yasuyuki Watanabe, Shinichi Kageyama, Koji Oka, Isao Tawara
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Hematology
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Online Access:https://www.tandfonline.com/doi/10.1080/16078454.2024.2392908
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author Emiko Kashima
Yuka Sugimoto
Keiki Nagaharu
Eiko Ohya
Makoto Ikejiri
Yasuyuki Watanabe
Shinichi Kageyama
Koji Oka
Isao Tawara
author_facet Emiko Kashima
Yuka Sugimoto
Keiki Nagaharu
Eiko Ohya
Makoto Ikejiri
Yasuyuki Watanabe
Shinichi Kageyama
Koji Oka
Isao Tawara
author_sort Emiko Kashima
collection DOAJ
description Background: Chronic myelomonocytic leukemia is a clonal hematological disorder with an inherent risk of transformation to acute myeloid leukemia. Recently, there has been exponential discovery of molecular abnormalities in patients with chronic myelomonocytic leukemia. Some of these mutations independently contribute to a higher risk of transformation and result in inferior overall survival. Treatment strategies for patients undergoing blastic transformation in chronic myelomonocytic leukemia, especially after progressing on hypomethylating agents, are currently limited.Case presentation: We present a case of a 70-year-old male patient with chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation following azacitidine monotherapy. Notably, he achieved hematological complete remission after the first course of venetoclax plus azacitidine, leading to the disappearance of RUNX1 mutation. We performed serial assessments of molecular analysis by next generation sequencing throughout his clinical course.Conclusion: The presence of RUNX1 mutation is associated with higher response rates to venetoclax-based combination therapies in chronic myelomonocytic leukemia with blastic transformation. Our findings suggest that even after azacitidine monotherapy, venetoclax plus azacitidine is effective in targeting leukemic clones harboring RUNX1 mutations. Furthermore, we emphasize the significance of molecular analysis, including next-generation sequencing, in providing insights into the detailed dynamics of clonal evolution and guiding treatment decisions.
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spelling doaj-art-f5d85abe6c814d99beee17cf8fcec58c2024-12-12T15:08:53ZengTaylor & Francis GroupHematology1607-84542024-12-0129110.1080/16078454.2024.2392908Venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with RUNX1 mutationEmiko Kashima0Yuka Sugimoto1Keiki Nagaharu2Eiko Ohya3Makoto Ikejiri4Yasuyuki Watanabe5Shinichi Kageyama6Koji Oka7Isao Tawara8Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, JapanDepartment of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, JapanDepartment of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, JapanDepartment of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, JapanDepartment of Clinical Laboratory, Mie University Hospital, Tsu, JapanDepartment of Hematology, Suzuka Kaisei Hospital, Suzuka, JapanDepartment of Hematology, Suzuka Kaisei Hospital, Suzuka, JapanDepartment of Hematology, Suzuka Kaisei Hospital, Suzuka, JapanDepartment of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, JapanBackground: Chronic myelomonocytic leukemia is a clonal hematological disorder with an inherent risk of transformation to acute myeloid leukemia. Recently, there has been exponential discovery of molecular abnormalities in patients with chronic myelomonocytic leukemia. Some of these mutations independently contribute to a higher risk of transformation and result in inferior overall survival. Treatment strategies for patients undergoing blastic transformation in chronic myelomonocytic leukemia, especially after progressing on hypomethylating agents, are currently limited.Case presentation: We present a case of a 70-year-old male patient with chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation following azacitidine monotherapy. Notably, he achieved hematological complete remission after the first course of venetoclax plus azacitidine, leading to the disappearance of RUNX1 mutation. We performed serial assessments of molecular analysis by next generation sequencing throughout his clinical course.Conclusion: The presence of RUNX1 mutation is associated with higher response rates to venetoclax-based combination therapies in chronic myelomonocytic leukemia with blastic transformation. Our findings suggest that even after azacitidine monotherapy, venetoclax plus azacitidine is effective in targeting leukemic clones harboring RUNX1 mutations. Furthermore, we emphasize the significance of molecular analysis, including next-generation sequencing, in providing insights into the detailed dynamics of clonal evolution and guiding treatment decisions.https://www.tandfonline.com/doi/10.1080/16078454.2024.2392908Chronic myelomonocytic leukemiablastic transformationvenetoclaxRUNX1next-generation sequencing
spellingShingle Emiko Kashima
Yuka Sugimoto
Keiki Nagaharu
Eiko Ohya
Makoto Ikejiri
Yasuyuki Watanabe
Shinichi Kageyama
Koji Oka
Isao Tawara
Venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation
Hematology
Chronic myelomonocytic leukemia
blastic transformation
venetoclax
RUNX1
next-generation sequencing
title Venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation
title_full Venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation
title_fullStr Venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation
title_full_unstemmed Venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation
title_short Venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation
title_sort venetoclax is effective for chronic myelomonocytic leukemia blastic transformation with runx1 mutation
topic Chronic myelomonocytic leukemia
blastic transformation
venetoclax
RUNX1
next-generation sequencing
url https://www.tandfonline.com/doi/10.1080/16078454.2024.2392908
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