Editorial Material
Cell & Tissue Engineering
Michael Spencer Chapman, Jyoti Nangalia
Summary: The study demonstrates that most allogeneic hematopoietic stem cells do not acquire additional somatic mutations post-transplantation, but suggests that the antiviral drug ganciclovir may contribute to some post-transplant malignancies through somatic mutagenesis.
Article
Multidisciplinary Sciences
Xujie Zhao, Ping Wang, Jonathan D. Diedrich, Brandon Smart, Noemi Reyes, Satoshi Yoshimura, Jingliao Zhang, Wentao Yang, Kelly Barnett, Beisi Xu, Zhenhua Li, Xin Huang, Jiyang Yu, Kristine Crews, Allen Eng Juh Yeoh, Marina Konopleva, Chia-Lin Wei, Ching-Hon Pui, Daniel Savic, Jun J. Yang
Summary: FLT3 is overexpressed in ZNF384-rearranged ALL, with exclusive activation of an intergenic enhancer element at the FLT3 locus and global enrichment of active enhancers within ZNF384 binding sites. Downregulation of ZNF384 decreases FLT3 activation and sensitizes ALL cells to FLT3 inhibitor gilteritinib. Moreover, gilteritinib shows significant anti-leukemia efficacy as a monotherapy in patient-derived xenograft models of ZNF384-rearranged ALL.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Wen Hao Neo, Michael Lie-A-Ling, Muhammad Zaki Hidayatullah Fadlullah, Georges Lacaud
Summary: During ontogeny, the establishment of the hematopoietic system occurs in different phases, from the yolk sac to the main arteries of the embryo. It has been discovered that yolk sac cells, initially thought to only bridge the gap to hematopoietic stem cells (HSCs), also play a role in embryonic organogenesis. Some of these cells persist into adulthood as distinct hematopoietic populations, opening up a new area of research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Roshana Thambyrajah, Anna Bigas
Summary: This review discusses the role of the Notch signaling pathway in hematopoietic cell fate specification and HSC activity. By studying different hematopoietic models, including zebrafish, mouse, and in vitro differentiated stem cells, we can understand the temporal and spatial regulation of Notch signaling during HSC development.
Article
Biochemistry & Molecular Biology
Hui Yang, Pinpin Sui, Ying Guo, Shi Chen, Marie E. Maloof, Guo Ge, Francine Nihozeko, Caroline R. Delma, Ganqian Zhu, Peng Zhang, Zhenqing Ye, Edward A. Medina, Nagi G. Ayad, Ruben Mesa, Stephen D. Nimer, Cheng-Ming Chiang, Mingjiang Xu, Yidong Chen, Feng-Chun Yang
Summary: This study reveals that deletion of Brd4 affects the self-renewal and differentiation of HSCs, leading to cell cycle arrest and senescence. The deletion of Brd4 results in increased chromatin accessibility and upregulation of senescence-specific genes. However, re-expression of BRD4 can rescue these effects by reducing H3 clipping and suppressing senescence gene expression.
Article
Hematology
Tim Sauer, Kathan Parikh, Sandhya Sharma, Bilal Omer, David Sedloev, Qian Chen, Linus Angenendt, Christoph Schliemann, Michael Schmitt, Carsten Mueller-Tidow, Stephen Gottschalk, Cliona M. Rooney
Summary: CD70 is a promising target antigen for AML treatment, and CD70-CAR T cells demonstrate good proliferation and antitumor activity in vitro and in vivo for CD70-positive AML patients, showing potential as a new treatment strategy.
Article
Immunology
Gerel Melig, Ikuo Nobuhisa, Kiyoka Saito, Ryota Tsukahara, Ayumi Itabashi, Yoshiakira Kanai, Masami Kanai-Azuma, Mitsujiro Osawa, Motohiko Oshima, Atsushi Iwama, Tetsuya Taga
Summary: In this study, it was found that Sox17 regulates the expression of Rasip1 gene by binding to its enhancer element, and the overexpression of Rasip1 increases hematopoietic activity. Conversely, the knockdown of Rasip1 decreases hematopoietic activity and cluster formation in Sox17-transduced cells.
INFLAMMATION AND REGENERATION
(2023)
Article
Multidisciplinary Sciences
Toshihiko Oki, Francois Mercier, Hiroki Kato, Yookyung Jung, Thomas O. McDonald, Joel A. Spencer, Michael C. Mazzola, Nick van Gastel, Charles P. Lin, Franziska Michor, Toshio Kitamura, David T. Scadden
Summary: This study investigates the real-time dynamics of the mTORC1 pathway in relation to AML growth and response to chemotherapy using fluorescent markers, showing a decrease and subsequent increase in mTORC1 activity with AML progression and maximal chemotherapy response, respectively. Data also suggests that chemotherapy induces mTORC1 activity, and timed inhibition of mTORC1 enhances killing of AML cells. These findings provide insights for targeted intervention strategies in AML treatment.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Olivia Arnold, Karina Barbosa, Aniruddha J. Deshpande, Nan Zhu
Summary: DOT1L plays a crucial role in normal and malignant hematopoiesis, and its aberrant activity is implicated in the development of hematopoietic malignancies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Andreas Lodberg
Summary: This article discusses the potential anabolic and stimulatory effects of inhibiting the transforming growth factor beta superfamily in muscle, blood, and bone. New therapeutic substances targeting activin, myostatin, and growth differentiation factor 11 signaling pathways offer hope for tissue deterioration. Additionally, a proposed classification of activin receptor signaling pathway inhibitors (IASPs) aims to provide a tool for researchers and clinicians to tailor therapy based on functionality and side effects.
CYTOKINE & GROWTH FACTOR REVIEWS
(2021)
Article
Oncology
Musa Yilmaz, Hagop Kantarjian, Nicholas J. Short, Patrick Reville, Marina Konopleva, Tapan Kadia, Courtney DiNardo, Gautam Borthakur, Naveen Pemmaraju, Abhishek Maiti, Elias Jabbour, Nitin Jain, Ghayas Issa, Koichi Takahashi, Koji Sasaki, Maro Ohanian, Sherry Pierce, Guillin Tang, Sanam Loghavi, Keyur Patel, Sa A. Wang, Guillermo Garcia-Manero, Michael Andreeff, Farhad Ravandi, Naval Daver
Summary: In older/unfit newly diagnosed patients with FLT3 mutated AML, lower intensity chemotherapy in combination with either a FLT3 inhibitor or with venetoclax results in improved overall survival rates.
BLOOD CANCER JOURNAL
(2022)
Article
Medicine, Research & Experimental
Zhou Yu, Jiaying Du, Hui Hui, Shaoxin Kan, Tongxin Huo, Kai Zhao, Tao Wu, Qinglong Guo, Na Lu
Summary: The study identified LT-171-861 as a potent FLT3 inhibitor and demonstrated its antitumor effects in AML, providing a rationale for future clinical trials in AML patients with FLT3-ITD mutations.
Article
Pharmacology & Pharmacy
Fangfang Wang, Jingcao Huang, Tingting Guo, Yuhuan Zheng, Li Zhang, Dan Zhang, Fujue Wang, Duolan Naren, Yushan Cui, Xiaoyan Liu, Ying Qu, Hongmei Luo, Yan Yang, Haichen Wei, Yong Guo
Summary: The combination treatment of HHT with quizartinib has shown synergistic effects on inhibiting cell growth, inducing apoptosis, and prolonging survival in mice with FLT3-ITD AML, suggesting it as a promising therapeutic strategy.
BIOCHEMICAL PHARMACOLOGY
(2021)
Editorial Material
Hematology
Sara E. Meyer
Summary: In this issue of Blood, Li et al.1 explore the role of FLT3 internal tandem duplication (ITD) in orchestrating transcriptional and epigenetic programs in myeloid progenitor cells, resulting in distinct functional outputs.
Article
Hematology
Ilaria Iacobucci, Chunxu Qu, Elena Varotto, Laura J. Janke, Xu Yang, Aman Seth, Anang Shelat, Jake D. Friske, Reiji Fukano, Jiyang Yu, Burgess B. Freeman, James A. Kennedy, Adam S. Sperling, Rena Zheng, Yingzhe Wang, Harini Jogiraju, Kirsten M. Dickerson, Debbie Payne-Turner, Sarah M. Morris, Emily S. Hollis, Nina Ghosn, Georgia E. Haggard, R. Coleman Lindsley, Benjamin L. Ebert, Charles G. Mullighan
Summary: Multiplexed genome editing in mouse hematopoietic cells led to the development of preclinical models for acute erythroid leukemia (AEL) and non-erythroid acute leukemia, highlighting the central role of mutational cooperativity in phenotype determination and clonal evolution. Clonal expansion during tumor evolution was driven by mutational cooccurrence, and mouse and human AEL exhibited deregulation of genes regulating erythroid development. Drug sensitivity was associated with the leukemia genotype, showing therapeutic potential for specific combinations of mutations in AEL.
Article
Multidisciplinary Sciences
Juan Carlos Yam-Puc, Lingling Zhang, Raul A. Maqueda-Alfaro, Laura Garcia-Ibanez, Yang Zhang, Jessica Davies, Yotis A. Senis, Michael Snaith, Kai-Michael Toellner
Summary: The study found that BCR signaling not only influences B cell selection and proliferation, but also can trigger cell apoptosis and suppress affinity maturation in the long term.
Article
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: Self-maintaining hematopoietic stem cells are susceptible to malignant transformation and serve as the cell-of-origin for certain leukemias. Tissue-specific stem cells replenish functional cells in specific tissues. Leukemias require at least two genomic insults, with one leading to dysregulation of hematopoietic stem cells, resulting in restricted cell lineage differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Immunology
Yang Zhang, Kai-Michael Toellner
Summary: Liu et al. demonstrate in this study that T cell-independent germinal centers can generate long-lived memory cells and plasma cell output, which may explain the long-term protection provided by polysaccharide antigens.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: The hematopoietic cell system is a complex ecosystem that can meet the needs of mature blood cells in both steady-state and emergency situations. It is highly integrated and social, adapting to different demands by generating cells biased towards specific lineages. Leukemia stem cells disrupt the cell hierarchy, being restricted to one lineage and able to alter the bone marrow stromal niches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: There is a need for agents to target cancer stem cells in order to effectively treat cancer and prevent relapse and metastasis, as conventional therapies often spare these cells. Targeting retinoic acid receptor (RAR)gamma is a promising approach, as it is selectively expressed in primitive cells and has been implicated in various human cancers. Antagonizing RAR gamma shows potential in inducing necroptosis in cancer stem cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Aysegul Erdem, Silvia Marin, Diego A. Pereira-Martins, Roldan Cortes, Alan Cunningham, Maurien G. Pruis, Bauke de Boer, Fiona A. J. van den Heuvel, Marjan Geugien, Albertus T. J. Wierenga, Annet Z. Brouwers-Vos, Eduardo M. Rego, Gerwin Huls, Marta Cascante, Jan Jacob Schuringa
Summary: This study uncovers the metabolic heterogeneity of acute myeloid leukemia (AML) and identifies Pyruvate dehydrogenase kinase 1 (PDK1) as a targetable determinant of different metabolic states in distinct subtypes of AML. This finding provides potential targets for the treatment of AML, a genetically heterogeneous disease.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Aysegul Erdem, Silvia Marin, Diego A. Pereira-Martins, Marjan Geugien, Alan Cunningham, Maurien G. Pruis, Isabel Weinhauser, Albert Gerding, Barbara M. Bakker, Albertus T. J. Wierenga, Eduardo M. Rego, Gerwin Huls, Marta Cascante, Jan Jacob Schuringa
Summary: This study reveals that FLT3-ITD + acute myeloid leukemia cells rely on oxidative phosphorylation and inhibition of complex II activity leads to increased lactate influx, driving respiration and providing a targetable vulnerability.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Andrzej Kutner, Geoffrey Brown, Eniko Kallay
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Teresa Zolek, Kaori Yasuda, Geoffrey Brown, Toshiyuki Sakaki, Andrzej Kutner
Summary: By studying the 3D structure of the vitamin D-metabolizing enzyme CYP3A4, we can predict and explain its metabolic conversion of analogs of 1,25D2. This is highly important for the design of stable vitamin D-based drug candidates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Alan Cunningham, Aysegul Erdem, Islam Alshamleh, Marjan Geugien, Maurien Pruis, Diego Antonio Pereira-Martins, Fiona A. J. van den Heuvel, Albertus T. J. Wierenga, Hilde ten Berge, Robin Dennebos, Vincent van den Boom, Shanna M. Hogeling, Isabel Weinhauser, Ruth Knops, Pim de Blaauw, M. Rebecca Heiner-Fokkema, Carolien Woolthuis, Ulrich L. Guenther, Eduardo M. Rego, Joost H. A. Martens, Joop H. Jansen, Harald Schwalbe, Gerwin Huls, Jan Jacob Schuringa
Summary: Targeting altered tumor cell metabolism, specifically methionine depletion, can be an effective therapeutic approach for acute myeloid leukemia (AML). Methionine is primarily used for protein translation and histone methylation, and its depletion leads to various cellular damages, including reduced RNA levels and enhanced apoptosis. Dietary methionine starvation delays AML progression.
Article
Biology
Nuria Vilaplana-Lopera, Vincent Cuminetti, Ruba Almaghrabi, Grigorios Papatzikas, Ashok Kumar Rout, Mark Jeeves, Elena Gonzalez, Yara Alyahyawi, Alan Cunningham, Aysegul Erdem, Frank Schnutgen, Manoj Raghavan, Sandeep Potluri, Jean-Baptiste Cazier, Jan Jacob Schuringa, Michelle A. C. Reed, Lorena Arranz, Ulrich L. Guenther, Paloma Garcia
Summary: This study identifies a novel metabolic crosstalk between AML and stromal cells, where AML cells stimulate stromal cells to secrete acetate for their own consumption. Transcriptome analysis and metabolic NMR analysis show that stromal cells exhibit a higher rate of glycolysis when co-cultured with AML cells. It is also found that acetate in stromal cells is derived from pyruvate via chemical conversion under the influence of reactive oxygen species (ROS) transferred from AML cells via gap junctions.
Review
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: The origin cell of chronic myeloid leukemia is a hematopoietic stem cell and the hallmark oncogene is BCR-ABLp210, which influences hematopoietic stem and progenitor cells to myeloid fate. Studies have shown that BCR-ABLp210 affects the epigenome, leading to dysregulation of fate choice for hematopoietic stem cells, but the reason why neutrophils are abundantly produced in the disease remains unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: All-trans retinoic acid plays a role in embryogenesis and also acts as a teratogen. The deregulation of cytosolic aldehyde dehydrogenases in various human cancers affects the synthesis of all-trans retinoic acid. Inhibiting these enzymes reduces cancer cell proliferation, induces apoptosis, and enhances chemotherapeutic sensitivity. RAR gamma is an oncogene in several types of cancer, and inhibiting its action leads to cancer cell death. Targeting the retinoic acid pathway shows promise in eliminating cancer stem cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Andrzej Kutner, Geoffrey Brown, Eniko Kallay
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Biochemistry & Molecular Biology
Carolina Vicente-Duenas, Isidro Sanchez-Garcia, Geoffrey Brown
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
