Review
Oncology
Sabine Blum, Gerasimos Tsilimidos, Helena Bresser, Michael Luebbert
Summary: Myelodysplasic syndromes (MDS) mainly occur in the elderly population, and most patients are too old or frail for intensive treatment. The current gold standard is treatment with hypomethylating agents, but the combination of hypomethylating agents with venetoclax has become the new gold standard for elderly and frail patients unable to undergo intensive treatment.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Qingyu Xu, Alexander Streuer, Johann-Christoph Jann, Eva Altrock, Nanni Schmitt, Johanna Flach, Carla Sens-Albert, Felicitas Rapp, Julia Wolf, Verena Nowak, Nadine Weimer, Julia Oblaender, Iris Palme, Mariia Kuzina, Ahmed Jawhar, Ali Darwich, Cleo-Aron Weis, Alexander Marx, Patrick Wuchter, Victor Costina, Evelyn Jaeger, Elena Sperk, Michael Neumaier, Alice Fabarius, Georgia Metzgeroth, Florian Nolte, Laurenz Steiner, Pavel A. Levkin, Mohamad Jawhar, Wolf-Karsten Hofmann, Vladimir Riabov, Daniel Nowak
Summary: Limited response rates and frequent relapses during standard of care in myelodysplastic neoplasms (MN) call for urgent improvement. In this study, the combination of 5-azacytidine (5-AZA) with PXS-5505 showed superior restoration of erythroid differentiation in MN patients, as compared to 5-AZA alone. This effect depended on direct contact with bone marrow stroma components and integrin signaling. Animal models further confirmed the efficacy of the combination treatment, indicating its potential for anemic MN.
NATURE COMMUNICATIONS
(2023)
Review
Hematology
Virginia O. Volpe, Rami S. Komrokji
Summary: Myelodysplastic syndromes (MDS) are characterized by bone-marrow failure, with anemia as the most common cytopenia in low-risk MDS patients. Current treatment options for MDS have limited durable responses and significant adverse effects, with chronic transfusions carrying risks. Luspatercept, a recently approved therapy for LR-MDS with ring sideroblasts, has shown improvement in transfusion independence with a well-tolerated safety profile.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2021)
Review
Medicine, General & Internal
Mikkael A. Sekeres, Justin Taylor
Summary: MDS is a hematopoietic malignancy with bone marrow dysplasia and decreased blood cell numbers. Treatment varies based on disease characteristics, from supportive care to hypomethylating agents for high-risk patients. Hematopoietic cell transplantation is potentially curative for high-risk MDS.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Biochemistry & Molecular Biology
Shuang Zheng, Jiaming Song, Dongli Linghu, Riyao Yang, Boning Liu, Zhen Xue, Qihui Chen, Chengjie Liu, Diansheng Zhong, Mien-Chie Hung, Linlin Sun
Summary: Gal-9 acts as an immunosuppressive regulator in the tumor microenvironment, and combination therapy targeting Gal-9 and ATM shows promising potential for cancer immunotherapy. Induction of Gal-9 via the STING/IFN β signaling pathway is an important mechanism mediating tumor immune escape.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Editorial Material
Hematology
Andrew H. Wei, John F. Seymour
Summary: This study compared the outcomes of adding lenalidomide, valproic acid, or idarubicin to azacitidine in the treatment of patients with higher-risk myelodysplastic syndromes using a randomized 'pick-a-winner' study design.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Cell Biology
Yasmin Abaza, Amer M. Zeidan
Summary: Immune checkpoint inhibitors have had a significant impact on the treatment of solid tumors, but there has been limited progress in myeloid malignancies. The low mutational burden of acute myeloid leukemia is a potential reason for the lack of response to T-cell harnessing ICIs. Targeting agents, such as magrolimab and sabatolimab, in combination with other drugs, have shown promising activity in early clinical trials.
Article
Cell Biology
Xi Zhang, Peng Huang, Liqiong Wang, Shu Chen, Basappa Basappa, Tao Zhu, Peter E. Lobie, Vijay Pandey
Summary: Loss of PTEN in endometrial carcinoma cells increases phosphorylation of BADSer99 (BADS99). Inhibition of BADS99 phosphorylation enhances apoptosis and reduces cell viability in PTEN-deficient EC cells. Combined inhibition of BADS99 phosphorylation and PARP improves the prognosis of recurrent EC patients by promoting apoptosis and DNA damage.
CELL DEATH & DISEASE
(2022)
Review
Pharmacology & Pharmacy
Kristina Simonicova, Lubos Janotka, Helena Kavcova, Zdena Sulova, Albert Breier, Lucia Messingerova
Summary: Resistance to hypomethylating agents is a major obstacle in the treatment of elderly patients with MDS and AML, with approximately 50% of patients not responding due to intrinsic resistance. Various mechanisms such as changes in drug transport, metabolism, and DNA repair contribute to drug resistance, highlighting the need for further research to address this issue.
DRUG RESISTANCE UPDATES
(2022)
Review
Oncology
Russell Lewis, Jan Philipp Bewersdorf, Amer M. Zeidan
Summary: For patients with LR-MDS, the goal is to alleviate symptoms and reduce transfusion burden associated with anemia. In addition to traditional treatments like supportive transfusions and ESAs, there are other therapeutic options available, such as luspatercept and lenalidomide, with novel agents like imetelstat and roxadustat in development.
CANCER MANAGEMENT AND RESEARCH
(2021)
Review
Hematology
Pongthep Vittayawacharin, Piyanuch Kongtim, Stefan O. Ciurea
Summary: Myelodysplastic syndromes (MDS) are a group of diverse hematopoietic stem cell tumors primarily affecting older individuals, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment. In recent years, the use of reduce-intensity conditioning regimens and haploidentical donors for transplantation has improved treatment outcomes. However, treatment-related mortality remains a limitation, highlighting the importance of pre-transplant evaluation for older patients.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jinal A. Patel, Camryn Zezelic, Julie Rageul, Joanne Saldanha, Arafat Khan, Hyungjin Kim
Summary: This study reveals the importance of TIM in preserving the structure of DNA replication forks and supporting seamless fork progression. It also demonstrates that TIM degradation triggers ATR-CHK1 checkpoint activation, leading to replication catastrophe and cell death. These findings highlight the potential of targeting TIM with ATR inhibitors for cancer therapy.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Katharina M. Ewers, Shilpa Patil, Waltraut Kopp, Juergen Thomale, Tabea Quilitz, Anna Magerhans, Xin Wang, Elisabeth Hessmann, Matthias Dobbelstein
Summary: Pancreatic cancer cells show varied sensitivities to cisplatin, with some being sensitive due to high expression of GATA6 and microRNA 200, while others can be sensitized by inhibiting HSP90. The combination of cisplatin and HSP90 inhibitors has shown promise in improving treatment outcomes for PDAC.
Letter
Cell & Tissue Engineering
Hongbo Zhu, Guangjia Feng, Na Zhao, Lei Wu, Zhiguo Long
Summary: This study analyzed the variants and DNA methylation patterns of cfDNA in patients with MDS and found that HRM had more SNPs and variants affecting amino acid sequences compared to LRM and the control group. HRM also showed higher levels of global DNA methylation on non-CpG sites. Candidate genes with specific variants and abnormal methylation were identified as potential biomarkers for diagnosing HRM and LRM.
CELL TRANSPLANTATION
(2022)
Article
Oncology
M. Cabezon, R. Malinverni, J. Bargay, B. Xicoy, S. Marce, A. Garrido, M. Tormo, L. Arenillas, R. Coll, J. Borras, M. J. Jimenez, M. Hoyos, D. Valcarcel, L. Escoda, F. Vall-Llovera, A. Garcia, L. L. Font, E. Ramila, M. Buschbeck, L. Zamora
Summary: The study suggests that altered DNA methylation patterns at specific CpG sites at diagnosis may serve as a biomarker for predicting the response to AZA and survival.
CLINICAL EPIGENETICS
(2021)
Article
Oncology
Daisuke Shinoda, Yaeko Nakajima-Takagi, Motohiko Oshima, Shuhei Koide, Kazumasa Aoyama, Atsunori Saraya, Hironori Harada, Bahityar Rahmutulla, Atsushi Kaneda, Kiyoshi Yamaguchi, Yoichi Furukawa, Haruhiko Koseki, Kazuya Shimoda, Tomoaki Tanaka, Goro Sashida, Atsushi Iwama
Summary: The insufficiency of PRC1.1, a component of polycomb repressive complex 1, promotes the development of myelofibrosis and acts as a tumor suppressor in this process. This impact is distinct from the effect of PRC2 insufficiency on the pathogenesis of myelofibrosis.
Article
Hematology
Satoshi Wakita, Masahiro Sakaguchi, Iekuni Oh, Shinichi Kako, Takashi Toya, Yuho Najima, Noriko Doki, Junya Kanda, Junya Kuroda, Shinichiro Mori, Atsushi Satake, Kensuke Usuki, Toshimitsu Ueki, Nobuhiko Uoshima, Yutaka Kobayashi, Eri Kawata, Kenji Tajika, Yuhei Nagao, Katsuhiro Shono, Motoharu Shibusawa, Jiro Tadokoro, Kensuke Kayamori, Masao Hagihara, Hitoji Uchiyama, Naoyuki Uchida, Yasushi Kubota, Shinya Kimura, Hisao Nagoshi, Tatsuo Ichinohe, Saiko Kurosawa, Sayuri Motomura, Akiko Hashimoto, Hideharu Muto, Eriko Sato, Masao Ogata, Kenjiro Mitsuhashi, Jun Ando, Atsushi Marumo, Ikuko Omori, Yusuke Fujiwara, Kazuki Terada, Shunsuke Yui, Kunihito Arai, Tomoaki Kitano, Miho Miyata, Akiyo Kurosawa, Ayumi Mizoguchi, Norio Komatsu, Takahiro Fukuda, Kazuteru Ohashi, Yoshinobu Kanda, Koiti Inokuchi, Hiroki Yamaguchi
Summary: Mutations of CCAAT/enhancer-binding protein alpha (CEBPAmu) significantly impact the prognosis of acute myeloid leukemia (AML). Particularly, CEBPAmu in the basic leucine zipper domain (bZIP) is strongly associated with a favorable prognosis and can serve as a potent marker for AML prognosis. This finding has implications for treatment stratification and the development of targeted therapeutic approaches in CEBPA-mutated AML.
Review
Biochemistry & Molecular Biology
Masayuki Yamashita, Atsushi Iwama
Summary: This review summarizes the changes in hematopoietic stem cells (HSCs) during aging and how different clones of HSCs can be expanded. Research shows that in mice and humans, the clonal behavior of HSCs is closely related to the risk of hematological malignancies and cardiovascular diseases. Therefore, understanding the impact of aging on the hematopoietic system is critical to prevent or overcome age-related changes in the blood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Shuhei Koide, Valgardur Sigurdsson, Visnja Radulovic, Kiyoka Saito, Zhiqian Zheng, Stefan Lang, Shamit Soneji, Atsushi Iwama, Kenichi Miharada
Summary: Isolation of long-term hematopoietic stem cell (HSC) is possible by utilizing flow cytometry with multiple cell surface markers. CD244 is identified as a potent marker to exclude non-functional HSCs and investigate the mechanism of HSC functional decline.
Article
Oncology
Koji Jimbo, Yaeko Nakajima-Takagi, Takahiro Ito, Shuhei Koide, Yasuhito Nannya, Atsushi Iwama, Arinobu Tojo, Takaaki Konuma
Summary: The role of Igsf8 in normal and malignant hematopoietic stem cells was investigated using a conditional knockout model. Deletion of Igsf8 improved survival in mouse myeloid leukemia models by depleting leukemia stem cells through enhanced apoptosis and beta-catenin degradation. Activation of beta-catenin in leukemia stem cells depends on Igsf8, which promotes the association of FZD4 with its co-receptor LRP6.
Article
Multidisciplinary Sciences
Naoki Itokawa, Motohiko Oshima, Shuhei Koide, Naoya Takayama, Wakako Kuribayashi, Yaeko Nakajima-Takagi, Kazumasa Aoyama, Satoshi Yamazaki, Kiyoshi Yamaguchi, Yoichi Furukawa, Koji Eto, Atsushi Iwama
Summary: The chromatin of aged hematopoietic stem cells (HSCs) undergoes changes that enhance their transcriptional responses to external stimuli. These changes are associated with the enrichment of stress-responsive enhancers in differentially accessible regions in the chromatin of aged HSCs. This study suggests that the responses of aged HSCs to external stimuli may be influenced by their exposure to previous or ongoing external stresses.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Shun Uemura, Masayuki Yamashita, Kazumasa Aoyama, Takako Yokomizo-Nakano, Motohiko Oshima, Miki Nishio, Masayoshi Masuko, Jun Takizawa, Hirohito Sone, Yasuhiro Yamada, Akira Suzuki, Atsushi Iwama
Summary: The study highlights the sex- and context-dependent roles of endothelial YAP1/TAZ in maintaining vascular integrity and organismal survival. EC-specific Yap1/Taz deletion compromises systemic vascular integrity, resulting in lethal circulation failure, and exacerbates systemic vascular dysfunction and circulation failure after sublethal radiation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Yusuke Isshiki, Motohiko Oshima, Naoya Mimura, Kensuke Kayamori, Yurie Miyamoto-Nagai, Masahide Seki, Yaeko Nakajima-Takagi, Takashi Kanamori, Eisuke Iwamoto, Tomoya Muto, Shokichi Tsukamoto, Yusuke Takeda, Chikako Ohwada, Sonoko Misawa, Jun-Ichiro Ikeda, Masashi Sanada, Satoshi Kuwabara, Yutaka Suzuki, Emiko Sakaida, Chiaki Nakaseko, Atsushi Iwama
Summary: POEMS syndrome is a rare monoclonal plasma cell disorder with unique features and unclear pathogenesis, but the recent study has provided new insights into the disease.
Meeting Abstract
Hematology
Asuka Shibamiya, Naoya Mimura, Yurie Miyamoto-Nagai, Shuhei Koide, Motohiko Oshima, Ola Rizq, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Kensuke Kayamori, Yusuke Isshiki, Nagisa Oshima-Hasegawa, Tomoya Muto, Shokichi Tsukamoto, Yusuke Takeda, Ryo Koyama-Nasu, Tetsuhiro Chiba, Hiroaki Honda, Koutaro Yokote, Atsushi Iwama, Emiko Sakaida
Letter
Biophysics
Shun-ichi Kimura, Hiroaki Shimizu, Takuya Miyazaki, Masatoshi Sakurai, Susumu Tanoue, Kensuke Kayamori, Chikako Ohwada, Kazuki Yoshimura, Hideki Nakasone, Takuma Ohashi, Katsuhiro Shono, Takayoshi Tachibana, Kaoru Hatano, Keigo Okada, Yuta Kimura, Sachiko Seo, Noriko Doki, Masatsugu Tanaka, Yoshihiro Hatta, Satoshi Takahashi, Yoshinobu Kanda
BONE MARROW TRANSPLANTATION
(2023)
Editorial Material
Hematology
Michael Y. He, Kensuke Kayamori
Summary: The study investigates the cellular response to vincristine, an important component of DLBCL treatment, using unbiased genome-wide CRISPR screening. The findings reveal promising targets and mechanisms for enhancing DLBCL treatment and advancing individualized approaches in clinical management.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Asuka Shibamiya, Yurie Miyamoto-Nagai, Shuhei Koide, Motohiko Oshima, Ola Rizq, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Rei Kato, Kensuke Kayamori, Yusuke Isshiki, Nagisa Oshima-Hasegawa, Tomoya Muto, Shokichi Tsukamoto, Yusuke Takeda, Ryo Koyama-Nasu, Tetsuhiro Chiba, Hiroaki Honda, Koutaro Yokote, Atsushi Iwama, Emiko Sakaida, Naoya Mimura
Summary: The study investigated the characteristics and significance of exhausted T cells in mature B cell neoplasms. The results showed an increase in PD-1(+) Tim-3(-) and PD-1(+) Tim-3(+) T cells in sick mice. PD-1(+) Tim-3(+) T cells exhibited cytotoxicity and short lifespan, resembling terminally exhausted T cells, while PD-1(+) Tim-3(-) T cells retained immunological responsiveness and stem-like features. The prevention of excessive T cell exhaustion may maintain effective anti-tumor immunity in mature B cell neoplasms.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Hematology
Alban Johansson, Dawn S. Lin, Francois E. Mercier, Masayuki Yamashita, Maziar Divangahi, Michael H. Sieweke
Summary: Immunologic memory is traditionally associated with the adaptive immune system, but recent studies show that hematopoietic stem cells and innate immune cells can acquire epigenetic changes to improve their response upon reinfection. This phenomenon, known as trained immunity, involves alterations in the epigenetic landscape and metabolic processes, resulting in the generation of epigenetically modified innate immune cells that provide enhanced protection against pathogens. This article summarizes the recent advancements in trained immunity and epigenetic memory formation in hematopoietic stem cells and alveolar macrophages.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Hematology
Juan A. Rubio-Lara, Kyomi J. Igarashi, Shubhankar Sood, Alban Johansson, Pia Sommerkamp, Masayuki Yamashita, Dawn S. Lin
Summary: Hematopoietic stem cells (HSCs) are crucial for the production of mature blood and immune cells. Ex vivo culture methods are essential for studying HSC biology and improving HSC therapies. This review discusses recent advances and technical considerations for three ex vivo HSC expansion methods.
EXPERIMENTAL HEMATOLOGY
(2023)