Review
Biochemistry & Molecular Biology
Moo-Kon Song, Byeong-Bae Park, Ji-Eun Uhm
Summary: FLT3 mutations are the most common genetic alterations in AML and have a negative impact on clinical prognosis. The development of FLT3 inhibitors has shown promise in improving outcomes for AML patients with FLT3 mutations. Midostaurin and gilteritinib have recently been approved as frontline treatments for AML by the FDA. Clinical trials are ongoing to explore the use of FLT3 inhibitors in different treatment settings. The accumulation of data on FLT3 inhibitors will be important evidence for guiding the use of these inhibitors in AML patients with FLT3 mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Chukwuebuka Egbuna, Kingsley C. Patrick-Iwuanyanwu, Eugene N. Onyeike, Johra Khan, Bader Alshehri
Summary: Mutations in FLT3 account for over 30-35% of AML cases, with current treatments providing only a 5-year average survival rate. Research is ongoing to discover new drug targets that may offer better outcomes for patients.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Cell Biology
Debora Bifano Pimenta, Vanessa Araujo Varela, Tarcila Santos Datoguia, Victoria Bulcao Caraciolo, Gabriel Herculano Lopes, Welbert Oliveira Pereira
Summary: Bone marrow is a complex tissue that regulates hematopoiesis, with AML developing in this microenvironment. Cells and molecules within the hematopoietic niche interact to influence leukemia development, suggesting that targeting the bone marrow microenvironment could be a promising strategy for AML treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Immunology
Thomas Menter, Alexandar Tzankov
Summary: This review examines the complex relationship between leukemic cells and the tumor microenvironment in AML, focusing on niche cells and T-cell subsets, and explores potential therapeutic strategies for manipulating the tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Javier Bregante, Anna Schoenbichler, Daniel Poeloeske, Lina Degenfeld-Schonburg, Garazi Monzo Contreras, Emir Hadzijusufovic, Elvin D. de Araujo, Peter Valent, Richard Moriggl, Anna Orlova
Summary: FLT3-ITD mutations are common and detrimental in AML, with AML cells quickly developing resistance to FLT3 kinase inhibitors. Through a drug screen, new potential therapeutics like ispinesib, WS6, ponatinib, and cabozantinib have been identified for FLT3-ITD+ AML. Combination therapy with cabozantinib and ispinesib shows strong efficacy against FLT3-ITD+ AML, suggesting promising novel treatment options for this clinical challenge.
Article
Hematology
Nianci Chen, Jiajia Pan, Yile Zhou, Liping Mao, Yinjun Lou, Jiejing Qian, Gaixiang Xu, Juying Wei, De Zhou, Lihong Shou, Li Huang, Minchao Yan, Hui Zeng, Cuihua Fan, Gongqiang Wu, Weiying Feng, Hongyan Tong, Jie Jin, Huafeng Wang
Summary: This retrospective analysis investigated the efficacy and safety of different gilteritinib-based combination therapies in relapsed/refractory FLT3-mutated AML patients. The study found that gilteritinib plus hypomethylating agent and venetoclax combination therapy showed higher response rates and may serve as an effective bridge to transplantation.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dan Ma, Ping Liu, Chujiao Hu, Zhen Zhou, Ping Wang, Yan Wang, Yaming Zhang, Yunsheng Ran, Pinghao Li, Jiangyuan Zhao, Jishi Wang, Chengliang Zhang, Lei Tang
Summary: This study revealed the important role of intracellular angiopoietin-1 (ANG-1) overexpression in drug resistance of chronic myeloid leukemia (CML), which promotes CML cell resistance through activation of the JAK/STAT pathway and enhancement of STAT5a phosphorylation. Therefore, intracellular ANG-1 may serve as a potential strategy for overcoming CML resistance.
Article
Biochemistry & Molecular Biology
Fansheng Ran, Yun Liu, Jian Zhu, Xuexian Deng, Hongmei Wu, Weizhi Tao, Xudong Xie, Yirong Hu, Yanan Zhang, Yong Ling
Summary: A novel class of aminopyrimidine-based dual-target inhibitors, designed for the treatment acute myeloid leukemia, effectively inhibited the activities of BTK, FLT3, and FLT3(D835Y) mutant. These compounds showed potent antiproliferative activities against leukemia cells and induced autophagy and apoptosis. In vivo studies demonstrated that compound 14m significantly suppressed the growth of MV-4-11 cells without apparent toxicity. These dual-target inhibitors hold promise for further optimization and mechanism studies.
BIOORGANIC CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Simona Soverini, Sara De Santis, Cecilia Monaldi, Samantha Bruno, Manuela Mancini
Summary: Chronic myeloid leukemia (CML) originates from the transformation of multipotent hematopoietic stem cells, with the resulting BCR-ABL1 fusion gene encoding a deregulated tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKIs) can eliminate progenitor cells but not quiescent LSCs. Researchers have been working on identifying druggable targets for LSC eradication in CML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Yosuke Tanaka, Reina Takeda, Tsuyoshi Fukushima, Keiko Mikami, Shun Tsuchiya, Moe Tamura, Keito Adachi, Terumasa Umemoto, Shuhei Asada, Naoki Watanabe, Soji Morishita, Misa Imai, Masayoshi Nagata, Marito Araki, Hitoshi Takizawa, Tomofusa Fukuyama, Chrystelle Lamagna, Esteban S. Masuda, Ryoji Ito, Susumu Goyama, Norio Komatsu, Tomoiku Takaku, Toshio Kitamura
Summary: Leukemia stem cells in chronic myeloid leukemia are resistant to imatinib, but can be eliminated by combining imatinib with IRAK1/4 inhibitors that inhibit the IRAK1/4-NF-kappa B-PD-L1 signaling pathway.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Emmanuella Oyogoa, Lukas Streich, Philipp W. Raess, Theodore Braun
Summary: This is a case report on a 27-year-old female with chronic myeloid leukemia (CML) who developed kinase-independent resistance and disease progression. The patient initially had chronic phase (CP) CML and acquired mutations in ASXL1 and RUNX1. Due to uncontrolled disease, she progressed to a chronic myelomonocytic leukemia-like (CMML) accelerated phase (AP) disease and obtained an IDH1 mutation. The disease progression was associated with the development of an inflammatory serositis, a phenomenon not typically observed in AP-CML.
FRONTIERS IN ONCOLOGY
(2023)
Article
Hematology
Peng Li, Shobi Venkatachalam, Daniela Ospina Cordona, Lorena Wilson, Tibor Kovacsovics, Karen A. Moser, Rodney R. Miles, David B. Beck, Tracy George, Srinivas K. Tantravahi
Summary: This article describes the characteristic hematologic findings in patients with VEXAS, including anemia, thrombocytopenia, and bone marrow hyperplasia. It provides awareness of the clinical and hematologic features of this disease, helping to improve the accuracy of diagnosis.
Article
Oncology
Mahran Shoukier, Tapan Kadia, Marina Konopleva, Ahmad S. Alotaibi, Mansour Alfayez, Sanam Loghavi, Keyur P. Patel, Rashmi Kanagal-Shamanna, Jorge Cortes, Bachar Samra, Elias Jabbour, Guillermo Garcia-Manero, Koichi Takahashi, Sherry Pierce, Nicholas J. Short, Musa Yilmaz, Koji Sasaki, Lucia Masarova, Naveen Pemmaraju, Gautam Borthakur, Hagop M. Kantarjian, Farhad Ravandi, Courtney D. DiNardo, Naval Daver
Summary: The combination of FLT3 inhibitor-based therapy with cytotoxic chemotherapy or low-intensity therapy appears to be effective in patients with FLT3-ITD/IDH co-mutated disease in both the frontline and recurrent and/or refractory settings. Fewer dual-mutated patients received cytotoxic chemotherapy or low-intensity therapy with an IDH1/2 inhibitor in the frontline setting; however, excellent responses also were observed with this approach.
Article
Multidisciplinary Sciences
Meike Farber, Yiyang Chen, Lucas Arnold, Michael Moellmann, Eva Boog-Whiteside, Yu-An Lin, H. Christian Reinhardt, Ulrich Duehrsen, Maher Hanoun
Summary: Targeting the interaction between leukemic cells and the microenvironment by inhibiting CD38 has the potential to enhance therapeutic efficacy in AML. However, while the anti-CD38 antibody daratumumab showed significant cytostatic efficacy in an in vitro model, it ultimately lacked robust anti-leukemic effects in vivo in a xenograft transplantation model.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Mohammad Houshmand, Nicoletta Vitale, Francesca Orso, Alessandro Cignetti, Ivan Molineris, Valentina Gaidano, Stefano Sainas, Marta Giorgis, Donatella Boschi, Carmen Fava, Alice Passoni, Marta Gai, Massimo Geuna, Federica Sora, Alessandra Iurlo, Elisabetta Abruzzese, Massimo Breccia, Olga Mulas, Giovanni Caocci, Fausto Castagnetti, Daniela Taverna, Salvatore Oliviero, Fabrizio Pane, Marco Lucio Lolli, Paola Circosta, Giuseppe Saglio
Summary: The study shows that the newly developed DHODH inhibitor, Meds433, is highly effective in targeting CML cells by activating the apoptotic pathway and inducing metabolic stress. This finding suggests that DHODH inhibition is a promising approach for targeting CML stem/progenitor cells.
CELL DEATH & DISEASE
(2022)
Letter
Hematology
Takashi Ishida, Tatsuro Jo, Shigeki Takemoto, Hitoshi Suzushima, Youko Suehiro, Ilseung Choi, Makoto Yoshimitsu, Yoshio Saburi, Kisato Nosaka, Atae Utsunomiya, Yukio Kobayashi, Kazuhito Yamamoto, Hiroshi Fujiwara, Kenji Ishitsuka, Shinichiro Yoshida, Naoya Taira, Kazunori Imada, Koji Kato, Yukiyoshi Moriuchi, Kenichi Yoshimura, Takeshi Takahashi, Kensei Tobinai, Ryuzo Ueda
BRITISH JOURNAL OF HAEMATOLOGY
(2019)
Article
Oncology
Akihiro Takeshita, Norio Asou, Yoshiko Atsuta, Toru Sakura, Yasunori Ueda, Masashi Sawa, Nobuaki Dobashi, Yasuhiro Taniguchi, Rikio Suzuki, Masaru Nakagawa, Shigehisa Tamaki, Maki Hagihara, Katsumichi Fujimaki, Hiroaki Furumaki, Yukako Obata, Hiroyuki Fujita, Masamitsu Yanada, Yoshinobu Maeda, Noriko Usui, Yukio Kobayashi, Hitoshi Kiyoi, Shigeki Ohtake, Itaru Matsumura, Tomoki Naoe, Yasushi Miyazaki
Article
Hematology
Kosuke Toyoda, Akiko Miyagi Maeshima, Junko Nomoto, Tomotaka Suzuki, Sayako Yuda, Nobuhiko Yamauchi, Hirokazu Taniguchi, Shinichi Makita, Suguru Fukuhara, Wataru Munakata, Dai Maruyama, Kensei Tobinai, Yukio Kobayashi
ANNALS OF HEMATOLOGY
(2019)
Article
Hematology
Motoko Yamaguchi, Ritsuro Suzuki, Kana Miyazaki, Jun Amaki, Jun Takizawa, Nodoka Sekiguchi, Shiori Kinoshita, Naoto Tomita, Hideho Wada, Yukio Kobayashi, Nozomi Niitsu, Toshihiko Ando, Takeshi Maeda, Bungo Saito, Hiroshi Matsuoka, Rika Sakai, Nobuko Kubota, Yasufumi Masaki, Yoshihiro Kameoka, Naoko Asano, Masahiko Oguchi, Naoyuki Katayama
ANNALS OF HEMATOLOGY
(2019)
Article
Hematology
Yukio Kobayashi
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2019)
Editorial Material
Hematology
Yukio Kobayashi
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2019)
Article
Oncology
Hitoshi Kiyoi, Joan D. Morris, Lekuni Oh, Yoshinobu Maeda, Hironobu Minami, Toshihiro Miyamoto, Toru Sakura, Hiroatsu Iida, Catherine A. Tuglus, Yuqi Chen, Cedric Dos Santos, James Kalabus, Abraham Anderson, Tomoko Hata, Yasuhiro Nakashima, Yukio Kobayashi
Article
Hematology
Masataka Ise, Hiromitsu Iizuka, Yoshimasa Kamoda, Masako Hirao, Michiko Kida, Kensuke Usuki
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2020)
Article
Hematology
Manabu Fujisawa, Tran B. Nguyen, Yoshiaki Abe, Yasuhito Suehara, Kota Fukumoto, Sakurako Suma, Kenichi Makishima, Chihiro Kaneko, Yen T. M. Nguyen, Kensuke Usuki, Kentaro Narita, Kosei Matsue, Naoya Nakamura, Shumpei Ishikawa, Fumihito Miura, Takashi Ito, Ayako Suzuki, Yutaka Suzuki, Seiya Mizuno, Satoru Takahashi, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Summary: This study investigates the mechanism by which TET2-mutant immune cells enable the development of Angioimmunoblastic T-cell lymphoma (AITL). The results reveal that Tet2-deficient immune cells play a crucial role in AITL development, and aberrant GCB cells in AITL undergo clonal evolution with recurrent mutations in genes related to core histones. Cd40-Cd40lg is identified as a possible mediator of interactions between GCB and tumor cell clusters.
Article
Hematology
Kensuke Usuki, Takayuki Ikezoe, Ken Ishiyama, Yoshinobu Kanda, Akihiko Gotoh, Hideo Hayashi, Akihiko Shimono, Akiyo Kitajima, Naoshi Obara, Jun-ichi Nishimura
Summary: Ravulizumab, a long-acting C5 inhibitor, has shown consistent safety and effectiveness in treating paroxysmal nocturnal hemoglobinuria (PNH) based on post-marketing surveillance data from 218 patients in Japan. Transfusion independence was less likely in patients with bone marrow failure.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Kensuke Usuki, Shigeki Ohtake, Sumihisa Honda, Mitsuhiro Matsuda, Atsushi Wakita, Yuichiro Nawa, Ken Takase, Akio Maeda, Nobuo Sezaki, Hisayuki Yokoyama, Satoru Takada, Daiki Hirano, Tatsuki Tomikawa, Masahiko Sumi, Shingo Yano, Hiroshi Handa, Shuichi Ota, Hiroyuki Fujita, Katsumichi Fujimaki, Atsuko Mugitani, Kensuke Kojima, Tomohiro Kajiguchi, Ko Fujimoto, Norio Asou, Noriko Usui, Yuichi Ishikawa, Akira Katsumi, Itaru Matsumura, Hitoshi Kiyoi, Yasushi Miyazaki
Summary: This report presents the results of a multicenter observational study on acute myeloid leukemia (AML) in Japan. The study registered 3728 AML patients, with 42% of them being younger than 65 years old and the male-to-female ratio being 1.57:1. The median follow-up time was 1807 days, and the estimated 5-year overall survival rate for AML patients was 31.1%. The study also found that trial-enrolled patients had a higher overall survival rate compared to non-enrolled patients, and women had a higher overall survival rate than men.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2023)
Article
Infectious Diseases
Hiroaki Shimizu, Yuho Najima, Shinichi Kako, Masatsugu Tanaka, Shin-ichiro Fujiwara, Takehiko Mori, Kensuke Usuki, Moritaka Gotoh, Maki Hagihara, Nobuhiro Tsukada, Makoto Oniduka, Satoru Takada, Emiko Sakaida, Shin Fujisawa, Masahiro Onoda, Nobuyuki Aotsuka, Shingo Yano, Kazuteru Ohashi, Satoshi Takahashi, Shinichiro Okamoto, Kanto Study Grp Cell Therapy KSGCT
Summary: Late CMV disease, defined as CMV disease occurring >100 days post-transplant, remains an important complication among allogeneic stem cell transplant recipients. Haploidentical related donor, adult T-cell leukemia lymphoma, and preemptive therapy before 100 days post-transplant were identified as independent risk factors for late CMV disease. Late CMV disease negatively affected transplant outcomes.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2023)
Meeting Abstract
Hematology
Tomotaka Suzuki, Suguru Fukuhara, Junko Nomoto, Satoshi Yamashita, Akiko Miyagi Maeshima, Yuta Ito, Shunsuke Hatta, Sayako Yuda, Shinichi Makita, Wataru Munakata, Tatsuya Suzuki, Dai Maruyama, Hirokazu Taniguchi, Toshikazu Ushijima, Koji Izutsu, Kensei Tobinai, Yukio Kobayashi
Meeting Abstract
Hematology
Akihiro Takeshita, Norio Asou, Yoshiko Atsuta, Hiroaki Furumaki, Toru Sakura, Yasunori Ueda, Masashi Sawa, Nobuaki Dobashi, Rikio Suzuki, Yasuhiro Taniguchi, Masaru Nakagawa, Shigehisa Tamaki, Maki Hagihara, Katsumichi Fujimaki, Yasuhisa Yokoyama, Hiroyuki Fujita, Masamitsu Yanada, Yoshinobu Maeda, Noriko Usui, Yukio Kobayashi, Hitoshi Kiyoi, Shigeki Ohtake, Itaru Matsumura, Tomoki Naoe, Yasushi Miyazaki
Meeting Abstract
Hematology
Yukio Kobayashi, Zachary F. Zimmerman, Iekuni Oh, Yoshinobu Maeda, Hironobu Minami, Toshihiro Miyamoto, Toru Sakura, Hiroatsu Iida, Yuqi Chen, Hitoshi Kiyoi