Review
Immunology
Tony Marchand, Sandra Pinho
Summary: Acute myeloid leukemia (AML) is a common type of leukemia in adults, with complete remission attainable in young and fit patients through intensive chemotherapy, but with frequent relapse and poor prognosis. Leukemic stem cells (LSCs) at the top of the hierarchy are thought to drive relapse due to their specific mutations and metabolic profile, which make them resistant to chemotherapy, as opposed to healthy hematopoietic stem cells (HSCs).
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Sweta B. Patel, Travis Nemkov, Angelo D'Alessandro, Robert S. Welner
Summary: This review discusses the metabolic differences between hematopoietic stem cells and leukemic stem cells in different leukemic models, and sheds light on the advancements and limitations of metabolic techniques in studying stem cell metabolism.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell & Tissue Engineering
Anna Bigas, Luis Galan Palma, Gayathri M. Kartha, Alessandra Giorgetti
Summary: Researchers have been studying embryonic stem cells for several decades, aiming to use them in regenerative medicine. The hematopoietic field has been a pioneer in utilizing stem cells for blood cell development and clinical applications. However, generating authentic hematopoietic stem cells has proven to be challenging. While progress has been made in understanding the origin of these cells during embryonic development, reproducing this process in the lab is still not possible. Nevertheless, knowledge gained from studying embryonic development is being applied to pluripotent stem cells derived from mice and humans. Additionally, studies have shown that hematopoietic cells derived from embryonic stem cells can recapitulate some leukemic transformation processes, making them valuable for modeling prenatal leukemia development and other leukemia-predisposing syndromes.
STEM CELLS TRANSLATIONAL MEDICINE
(2022)
Review
Oncology
Isabella Maria Mayer, Andrea Hoelbl-Kovacic, Veronika Sexl, Eszter Doma
Summary: Transplantation of adult hematopoietic stem cells is crucial for treating hematological disorders, while leukemic stem cells play a significant role in disease initiation and relapse. Understanding methods to maintain and expand hematopoietic cells, as well as isolate and enrich hematopoietic stem cells and leukemic stem cells, is essential for developing therapeutic strategies.
Review
Cell Biology
Ryota Yasui, Keisuke Sekine, Hideki Taniguchi
Summary: Efficient and strategic screening of cell culture conditions for PSCs, MSCs, HSCs, and CHO cells using design of experiments methods like factorial design and orthogonal array design is essential for academic and industrial applications aiming at disease modelling, drug screening, and regenerative medicine.
Article
Biochemistry & Molecular Biology
Ningfei An, Saira Khan, Molly K. K. Imgruet, Lia Jueng, Sandeep Gurbuxani, Megan E. E. McNerney
Summary: -7/del(7q) is commonly found in myeloid neoplasms. CUX1, located on 7q22, is a transcription factor associated with poor prognosis when mutated. CUX1 deficiency and oncogenic RAS mutations are found to be linked and promote leukemogenesis. This research indicates a potential therapy for malignancies with CUX1 inactivation.
Article
Chemistry, Multidisciplinary
Wariya Nirachonkul, Siriporn Ogonoki, Tarika Thumvijit, Supanimit Chiampanichayakul, Pawaret Panyajai, Songyot Anuchapreeda, Singkome Tima, Sawitree Chiampanichayakul
Summary: The study focused on formulating curcumin nanoparticles conjugated with anti-CD123 to target LSCs in AML, improving curcumin's bioavailability. Results showed that the formulation induced cytotoxicity and apoptosis in KG-1a cells, with higher uptake and cytotoxic effects observed in anti-CD123-Cur-NPs.
Article
Pharmacology & Pharmacy
Fahui Li, Congying Gao, Xueming Li, Jiangyun Wang, Yao Zhao, Yu Ke, Ying Liu, Hong-Min Liu, Zhenbo Hu, Liuya Wei, Zhe-Sheng Chen
Summary: The natural compound Jiyuan oridonin A (JOA) has been found to overcome the differentiation blockade in AML cells and leukemic stem-like cells, inhibiting their proliferation and offering a novel therapeutic strategy for AML.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell & Tissue Engineering
Huiying Ma, Tian Tian, Zhumei Cui
Summary: Ovarian cancer is a highly lethal gynecological malignancy characterized by tumor heterogeneity, limited early diagnosis methods, and high incidence of chemoresistant recurrent disease. Cancer stem cells (CSCs) play a crucial role in tumor growth, metastasis, and resistance to treatment. Understanding the role of CSCs in ovarian cancer can provide insights into the disease's progression and resistance mechanisms, leading to the development of novel therapeutic strategies. This review summarizes the current research on targeting ovarian cancer stem cells, including signaling pathways, markers, and drugs, with the aim of improving the management of ovarian cancer patients using CSC-based therapies.
STEM CELL RESEARCH & THERAPY
(2023)
Review
Oncology
Meixi Peng, Yongxiu Huang, Ling Zhang, Xueya Zhao, Yu Hou
Summary: Acute myeloid leukemia (AML) is a hematologic malignancy with poor prognosis, characterized by various cytogenetic and molecular abnormalities. Current treatments often fail to eliminate leukemic stem cells (LSCs), which exhibit a unique metabolic profile dependent on oxidative phosphorylation (OXPHOS). Understanding the regulation of OXPHOS in LSCs may lead to effective clinical therapies in AML.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Vera Weeda, Stefan G. C. Mestrum, Math P. G. Leers
Summary: This review provides an overview of immunophenotypic markers that can be used to identify leukemic blast cells in the bone marrow using multiparameter flow cytometry. While a single marker is not sufficient to differentiate between leukemic and normal blast cells, combinations of markers can enable such distinction. The identification of these markers has provided new perspectives for tailored clinical follow-up.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
He-Zhou Guo, Zi-Hua Guo, Shan-He Yu, Li-Ting Niu, Wan-Ting Qiang, Meng-Meng Huang, Yuan-Yuan Tian, Juan Chen, Hui Yang, Xiang-Qin Weng, Yi Zhang, Wu Zhang, Shao-Yan Hu, Jun Shi, Jiang Zhu
Summary: Abnormal IL-36 production in leukemic progenitor cells is a key feature of AML, promoting inflammation and preventing leukemia clearance by CD8(+) T cells. Chemotherapy-induced IL-36 production from residual leukemic cells allows for the persistence of an immunosuppressive axis post-treatment. Depletion of inflammatory monocytes, in combination with chemotherapy and PD-1 blockade, shows promise in restricting AML progression and relapse.
Article
Chemistry, Multidisciplinary
Kunxia Cao, Yangyang Du, Xin Bao, Mingda Han, Rui Su, Jiuxia Pang, Shujun Liu, Zhan Shi, Fei Yan, Shouhua Feng
Summary: In this study, FTO inhibitor-loaded GSH-bioimprinted nanocomposites were developed to selectively target leukemia cells, especially leukemia stem cells (LSCs), and induce cell death by disrupting intracellular redox status. Additionally, the nanocomposites increased m(6)A RNA modification levels and enhanced the efficacy of immune therapy.
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
Bin Zhang, Dandan Zhao, Fang Chen, David Frankhouser, Huafeng Wang, Khyatiben V. Pathak, Lei Dong, Anakaren Torres, Krystine Garcia-Mansfield, Yi Zhang, Dinh Hoa Hoang, Min-Hsuan Chen, Shu Tao, Hyejin Cho, Yong Liang, Danilo Perrotti, Sergio Branciamore, Russell Rockne, Xiwei Wu, Lucy Ghoda, Ling Li, Jie Jin, Jianjun Chen, Jianhua Yu, Michael A. Caligiuri, Ya-Huei Kuo, Mark Boldin, Rui Su, Piotr Swiderski, Marcin Kortylewski, Patrick Pirrotte, Le Xuan Truong Nguyen, Guido Marcucci
Summary: The mechanisms underlying the transformation of chronic phase (CP) to blast crisis (BC) in chronic myeloid leukemia (CML) are not fully understood. This study reveals that deficiency of miR-142 drives the progression of CML to BC by regulating mitochondrial metabolism, and it may serve as a potential therapeutic target to prevent BC in CML.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Desmond Wai Loon Chin, Tetsuichi Yoshizato, Stina Virding Culleton, Francesca Grasso, Magdalena Barbachowska, Seishi Ogawa, Sten Eirik W. Jacobsen, Petter S. Woll
Article
Immunology
Melinda Czeh, Sina Stable, Stephen Kramer, Lena Tepe, Sweta Talyan, Joana Carrelha, Yiran Meng, Barbara Heitplatz, Marius Schwabenland, Michael D. Milsom, Christoph Plass, Marco Prinz, Matthias Schlesner, Miguel A. Andrade-Navarro, Claus Nerlov, Sten Eirik W. Jacobsen, Daniel B. Lipka, Frank Rosenbauer
Summary: This study reveals the important role of DNA methylation in the development of dendritic cell subsets. Reduction of methylation can deplete plasmacytoid dendritic cells and alleviate systemic lupus erythematosus.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Muhammad Ali, Eirini Giannakopoulou, Yingqian Li, Madeleine Lehander, Stina Virding Culleton, Weiwen Yang, Cathrine Knetter, Mete Can Odabasi, Ravi Chand Bollineni, Xinbo Yang, Zsofia Foldvari, Maxi-Lu Boschen, Eli Taraldsrud, Erlend Stronen, Mireille Toebes, Amy Hillen, Stefania Mazzi, Arnoud H. de Ru, George M. C. Janssen, Arne Kolstad, Geir Erland Tjonnfjord, Benedicte A. Lie, Marieke Griffioen, Soren Lehmann, Liv Toril Osnes, Jochen Buechner, K. Christopher Garcia, Ton N. Schumacher, Peter A. van Veelen, Matthias Leisegang, Sten Eirik W. Jacobsen, Petter Woll, Johanna Olweus
Summary: T cells modified with TCRs targeting TdT can specifically eliminate acute lymphoblastic leukemia cells while sparing normal lymphocytes. TdT is highly expressed in cancer cells but transiently expressed in normal cells, thus limiting the toxicity of T cell targeting TdT.
NATURE BIOTECHNOLOGY
(2022)
Editorial Material
Oncology
Alexander E. Perl, Paresh Vyas
Summary: Two publications provide new insights into risk stratification in patients with acute myeloid leukemia and mutations in IDH1, IDH2, or FLT3 who received initial therapy with venetoclax and azacitidine, setting the stage for future trials integrating molecularly targeted therapy with this new standard regimen.
CLINICAL CANCER RESEARCH
(2022)
Article
Hematology
Stephane de Botton, Pau Montesinos, Andre C. Schuh, Cristina Papayannidis, Paresh Vyas, Andrew H. Wei, Hans Ommen, Sergey Semochkin, Hee-Je Kim, Richard A. Larson, Jaime Koprivnikar, Olga Frankfurt, Felicitas Thol, Joerg Chromik, Jenny Byrne, Arnaud Pigneux, Xavier Thomas, Olga Salamero, Maria Belen Vidriales, Vadim Doronin, Hartmut Doehner, Amir T. Fathi, Eric Laille, Xin Yu, Maroof Hasan, Patricia Martin-Regueira, Courtney D. DiNardo
Summary: This study compared the efficacy of the oral IDH2 inhibitor enasidenib with conventional care regimens (CCR) in older patients with late-stage mutant-IDH2 AML. Enasidenib significantly improved event-free survival, time to treatment failure, overall response rate, hematologic improvement, and transfusion independence compared to CCR. However, there was no significant difference in overall survival, possibly due to early dropout and subsequent AML-directed therapies.
Article
Hematology
Daniel A. Arber, Attilio Orazi, Robert P. Hasserjian, Michael J. Borowitz, Katherine R. Calvo, Hans-Michael Kvasnicka, Sa A. Wang, Adam Bagg, Tiziano Barbui, Susan Branford, Carlos E. Bueso-Ramos, Jorge E. Cortes, Paola Dal Cin, Courtney D. DiNardo, Herve Dombret, Eric J. Duncavage, Benjamin L. Ebert, Elihu H. Estey, Fabio Facchetti, Kathryn Foucar, Naseema Gangat, Umberto Gianelli, Lucy A. Godley, Nicola Gokbuget, Jason Gotlib, Eva Hellstrom-Lindberg, Gabriela S. Hobbs, Ronald Hoffman, Elias J. Jabbour, Jean-Jacques Kiladjian, Richard A. Larson, Michelle M. Le Beau, Mignon L. -C. Loh, Bob Lowenberg, Elizabeth Macintyre, Luca Malcovati, Charles G. Mullighan, Charlotte Niemeyer, Olatoyosi M. Odenike, Seishi Ogawa, Alberto Orfao, Elli Papaemmanuil, Francesco Passamonti, Kimmo Porkka, Ching-Hon Pui, Jerald P. Radich, Andreas Reiter, Maria Rozman, Martina Rudelius, Michael R. Savona, Charles A. Schiffer, Annette Schmitt-Graeff, Akiko Shimamura, Jorge Sierra, Wendy A. Stock, Richard M. Stone, Martin S. Tallman, Juergen Thiele, Hwei-Fang Tien, Alexandar Tzankov, Alessandro M. Vannucchi, Paresh Vyas, Andrew H. Wei, Olga K. Weinberg, Agnieszka Wierzbowska, Mario Cazzola, Hartmut Dohner, Ayalew Tefferi
Summary: In 2016, the WHO, Society for Hematopathology, and European Association for Haematopathology collaborated to update the classification of myeloid neoplasms and acute leukemias, advancing the field of myeloid neoplasms and acute leukemias.
Article
Multidisciplinary Sciences
Thomas R. Jackson, Aini Vuorinen, Laia Josa-Cullere, Katrina S. Madden, Daniel Conole, Thomas J. Cogswell, Isabel V. L. Wilkinson, Laura M. Kettyle, Douzi Zhang, Alison O'Mahony, Deanne Gracias, Lorna McCall, Robert Westwood, Georg C. Terstappen, Stephen G. Davies, Edward W. Tate, Graham M. Wynne, Paresh Vyas, Angela J. Russell, Thomas A. Milne
Summary: This study found that tubulin disruptors can induce differentiation of AML cells, leading to decreased tumor burden and increased survival rates in vivo.
Review
Oncology
Naval G. Daver, Abhishek Maiti, Tapan M. Kadia, Paresh Vyas, Ravindra Majeti, Andrew H. Wei, Guillermo Garcia-Manero, Charles Craddock, David A. Sallman, Hagop M. Kantarjian
Summary: TP53-mutated MDS and AML are a distinct group of myeloid disorders with poor outcomes. Recent advances have identified novel pathogenic mechanisms and emerging therapies, including immunotherapeutic and nonimmune-based approaches, for the treatment of this entity.
Article
Cell Biology
Yiran Meng, Joana Carrelha, Roy Drissen, Xiying Ren, Bowen Zhang, Adriana Gambardella, Simona Valletta, Supat Thongjuea, Sten Eirik Jacobsen, Claus Nerlov
Summary: The lymphoid fate in haematopoietic stem cells is determined through epigenetic programming rather than transcriptional control, which also influences the differentiation pathways of platelets with distinct kinetics.
NATURE CELL BIOLOGY
(2023)
Article
Hematology
Sylvie D. Freeman, Abin Thomas, Ian Thomas, Robert K. Hills, Paresh Vyas, Amanda Gilkes, Marlen Metzner, Niels Asger Jakobsen, Alison Kennedy, Rachel Moore, Nuria Marquez Almuina, Sarah Burns, Sophie King, Georgia Andrew, Kathleen M. E. Gallagher, Rob S. Sellar, Paul Cahalin, Duruta Weber, Mike Dennis, Priyanka Mehta, Steven Knapper, Nigel H. Russell
Summary: Addition of gemtuzumab ozogamicin to induction chemotherapy improves outcomes in older AML patients, especially those with MRD<0.1% and IDH mutations. The survival advantage from this treatment is dependent on allogeneic transplantation.
Article
Oncology
Naval G. Daver, Paresh Vyas, Suman Kambhampati, Monzr M. Al Malki, Richard A. Larson, Adam S. Asch, Gabriel Mannis, Wanxing Chai-Ho, Tiffany N. Tanaka, Terrence J. Bradley, Deepa Jeyakumar, Eunice S. Wang, Kendra Sweet, Hagop M. Kantarjian, Guillermo Garcia-Manero, Rami Komrokji, Guan Xing, Giridharan Ramsingh, Camille Renard, Joshua F. Zeidner, David A. Sallman
Summary: Magrolimab combined with azacitidine showed promising efficacy and tolerability in patients with untreated AML ineligible for intensive chemotherapy, including those with TP53 mutations.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Tiago C. Luis, Nikolaos Barkas, Joana Carrelha, Alice Giustacchini, Stefania Mazzi, Ruggiero Norfo, Bishan Wu, Affaf Aliouat, Jose A. Guerrero, Alba Rodriguez-Meira, Tiphaine Bouriez-Jones, Iain C. Macaulay, Maria Jasztal, Guangheng Zhu, Heyu Ni, Matthew J. Robson, Randy D. Blakely, Adam J. Mead, Claus Nerlov, Cedric Ghevaert, Sten Eirik W. Jacobsen
Summary: In this study, the researchers uncover a feedback mechanism in which IL-1 secreted by activated platelets signals through niche Lepr+ cells to activate HSCs and restore platelet homeostasis.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Hematology
Edyta Wojtowicz, Jayna Mistry, Vladimir Uzun, Anita Scoones, Desmond Chin, Laura Kettyle, Allegra Lord, Francesca Grasso, Graham Etherington, Charlotte Hellmich, Petter Woll, Mirjam Belderbos, Kristian Bowles, Leonid Bystrykh, Claus Nerlov, Wilfried Haerty, Sten Eirik Jacobsen, Stuart Rushworth, Iain Macaulay
EXPERIMENTAL HEMATOLOGY
(2022)
Meeting Abstract
Hematology
Yiran Meng, Joana Carrelha, Roy Drissen, Adriana Gambardella, Supat Thongjuea, Sten Eirik Jacobsen, Claus Nerlov
EXPERIMENTAL HEMATOLOGY
(2022)
Meeting Abstract
Hematology
Alba Rodriguez-Meira, Ruggiero Norfo, Wei Wen, Agathe Chedeville, Haseeb Rahman, Jennifer O'Sullivan, Guanlin Wang, Eleni Louka, Warren Kretzschmar, Aimee Paterson, Charlotte Brierley, Jean-Edouard Martin, Caroline Demeule, Matthew Bashton, Nikolaos Sousos, Angela Hamblin, Helene Guermouche, Florence Pasquier, Christophe Marzac, Francois Girodon, Mark Drummond, Claire Harrison, Isabelle Plo, Sten Eirik Jacobsen, Bethan Psaila, Supat Thongjuea, Ileana Antony-Debre, Adam Mead
EXPERIMENTAL HEMATOLOGY
(2022)
