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)
Review
Medicine, General & Internal
Salvatore Leotta, Annalisa Condorelli, Roberta Sciortino, Giulio Antonio Milone, Claudia Bellofiore, Bruno Garibaldi, Giovanni Schinina, Andrea Spadaro, Alessandra Cupri, Giuseppe Milone
Summary: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for high-risk acute myeloid leukemia (AML). Advances in pre-transplant induction therapies, supportive care, donor selection, and conditioning regimens have expanded the patient population eligible for HSCT. The introduction of novel agents and targeted therapies have enriched the treatment landscape for AML relapse after HSCT, while close monitoring of minimal-residual disease (MRD) and preemptive strategies have become essential in post-transplant care.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Oncology
Jennifer Marvin-Peek, Bipin N. Savani, Oluwole O. Olalekan, Bhagirathbhai Dholaria
Summary: CAR therapy has been effective in treating B-cell mediated cancers, but faces challenges in treating AML. This review discusses the difficulties in developing CAR therapy for AML and recent advances in the field. Continued improvement in AML CAR therapy would have a significant impact on this disease.
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
Shouyun Li, Xue Yang, Shuang Liu, Yirui Chen, Haiyan Xing, Kejing Tang, Zheng Tian, Yingxi Xu, Qing Rao, Min Wang, Jianxiang Wang
Summary: The study found that expression of TR in mouse hematopoietic progenitors induces blockade of differentiation with enhanced proliferative capacity in vitro and established a new mouse leukemia model that more accurately recapitulates human APL. Despite sensitivity to ATRA-induced cell differentiation, neither ATRA monotherapy nor combination with As2O3 confers survival benefit to TR mice, consistent with poor clinical outcomes of APL patients with the TR fusion gene. Based on histone deacetylation phenotypes implied by bioinformatic analysis, HDAC inhibitors demonstrated significant survival superiority in the survival of TR mice, providing insights into clinical efficacy against rare types of APL.
CELL DEATH & DISEASE
(2021)
Article
Biotechnology & Applied Microbiology
Ki Hyun Bae, Fritz Lai, Jamie Mong, Akiko Niibori-Nambu, Kiat Hwa Chan, Zhisheng Her, Motomi Osato, Min-Han Tan, Qingfeng Chen, Motoichi Kurisawa
Summary: This study presents a bone marrow-targetable green tea catechin-based micellar nanocomplex that synergistically enhances the anti-leukemic potency of sorafenib. It demonstrates effective eradication of leukemic blasts in bone marrow and improved survival rates in an AML-PDX mouse model.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Oncology
Jong-Mi Lee, Silvia Park, Insik Hwang, Dain Kang, Byung Sik Cho, Hee-Je Kim, Ari Ahn, Myungshin Kim, Yonggoo Kim
Summary: This article presents an ITD-tracing algorithm based on NGS method for monitoring MRD in AML patients. The assay shows high sensitivity and superior performance, and demonstrates prognostic value in AML patients undergoing allogeneic hematopoietic stem cell transplantation.
Article
Biochemistry & Molecular Biology
Xinping Huang, Yongfeng Yang, Dan Zhu, Yan Zhao, Min Wei, Ke Li, Hong-Hu Zhu, Xiaofeng Zheng
Summary: The research reveals that PRMT5 is highly expressed in APL patients and promotes APL by interacting with PML-RAR alpha. Inhibition of PRMT5 effectively blocks the growth of APL cells, and combined use with As2O3 shows promise as a therapeutic strategy against APL.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biology
Hae J. Park, Mark A. Gregory, Vadym Zaberezhnyy, Andrew Goodspeed, Craig T. Jordan, Jeffrey S. Kieft, James DeGregori
Summary: The bone marrow microenvironment provides protection to AML cells from FLT3 inhibitor drugs through the activation of ATM and upregulation of oxidative phosphorylation. Combination therapy with the mTOR inhibitor everolimus and the FLT3 inhibitor quizartinib effectively reduces tumor burden and prevents relapse in AML xenograft models.
Review
Oncology
Ying Li, Fang Zhou
Summary: This study systematically assesses the efficacy of hematopoietic stem cell transplantation (HSCT) and bone marrow transplantation (BMT) in treating acute myeloid leukemia (AML). Seven clinical controlled studies with 1280 samples were included. The meta-analysis results show that there is no significant difference in overall survival (OS) and disease-free survival (DFS) rates between the peripheral HSCT (PHSCT) group and the BMT group. The BMT group has lower incidence of acute graft-versus-host disease (GVHD), chronic GVHD, and disease recurrence. However, there is no noticeable difference in recurrence-related mortality and non-relapse-related mortality. Some funnel plots suggest possible publication bias due to small sample size and heterogeneity. In conclusion, BMT can be considered an effective treatment for AML patients, reducing recurrence and complications while ensuring a curative effect. Longer follow-up studies are needed to further support its clinical application.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Xuejing Shao, Yingqian Chen, Wei Wang, Wenxin Du, Xingya Zhang, Minyi Cai, Shaowei Bing, Ji Cao, Xiaojun Xu, Bo Yang, Qiaojun He, Meidan Ying
Summary: This study reveals a DUB-involved mechanism in regulating the stability of PML/RARα and develops a novel pharmacological approach to degrade PML/RARα by inhibiting DUB. The key DUB involved in this mechanism is identified as ovarian tumor protease YOD1. Inhibition of YOD1 promotes the degradation of PML/RARα and effectively inhibits the growth of APL cells.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Medicine, General & Internal
Mohammad Houshmand, Alireza Kazemi, Ali Anjam Najmedini, Muhammad Shahzad Ali, Valentina Gaidano, Alessandro Cignetti, Carmen Fava, Daniela Cilloni, Giuseppe Saglio, Paola Circosta
Summary: The elimination of TKI resistant leukemic stem cells is crucial for achieving long-term treatment free remission in CML patients. Understanding the biology of LSCs and identifying differences from normal HSCs are important steps in designing strategies to target LSCs selectively.
JOURNAL OF CLINICAL MEDICINE
(2021)
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)
Article
Multidisciplinary Sciences
Sarah Ennis, Alessandra Conforte, Eimear O'Reilly, Javid Sabour Takanlu, Tatiana Cichocka, Sukhraj Pal Dhami, Pamela Nicholson, Philippe Krebs, Pilib O. Broin, Eva Szegezdi
Summary: In this study, a single-cell gene expression database of 339,381 bone marrow cells was established to comprehensively characterize the microenvironment of both healthy and acute myeloid leukemia (AML). Significant changes in cell type proportions and gene expression were observed in AML, indicating disruption of the entire niche. Predicted interactions between hematopoietic stem and progenitor cells (HSPCs) and other bone marrow cell types were also explored, revealing an expansion of interactions in AML that promote HSPC-cell adhesion, immunosuppression, and cytokine signaling. Transforming growth factor b1 (TGFB1)-related interactions were particularly widespread and were shown to drive AML cell quiescence in vitro. These findings highlight potential mechanisms of enhanced AML-HSPC competitiveness and a skewed microenvironment fostering AML growth.
Article
Chemistry, Analytical
Leiying Xie, Jie Wang, Na Wang, Jianguo Zhu, Qianqian Yin, Ruobing Guo, Junli Duan, Shaowei Wang, Changning Hao, Xuechu Shen
Summary: Acute myeloid leukemia (AML) is a highly mortal and recurrent hematologic malignancy. Traditional AML diagnosis methods are painful and burdensome for patients. This study develops a rapid and minimally invasive method using peripheral blood's infrared difference spectrum (IDS) to identify AML, providing a pain-free alternative.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Oncology
Katrina M. Lappin, Eliana M. Barros, Satpal S. Jhujh, Gareth W. Irwin, Hayley McMillan, Fabio G. Liberante, Cheryl Latimer, Melissa J. La Bonte, Ken Mills, D. Paul Harkin, Grant S. Stewart, Kienan Savage
Summary: Mutations in SF3B1 affect cellular response to DNA damage and increase sensitivity to ionizing radiation and chemotherapeutic agents. These mutations induce DNA damage and can be targeted with PARP inhibitors.
Article
Virology
Connor G. G. Bamford, Lindsay Broadbent, Elihu Aranday-Cortes, Mary McCabe, James McKenna, David G. Courtney, Olivier Touzelet, Ahlam Ali, Grace Roberts, Guillermo Lopez Campos, David Simpson, Conall McCaughey, Derek Fairley, Ken Mills, Ultan F. Power
Summary: This study finds that the evolution of SARS-CoV-2 is restrained in pediatric respiratory epithelial cells but still exhibits significant genetic plasticity shaped by both viral and host cell factors.
Article
Cell Biology
Ada-Sophia Clees, Verena Stolp, Bjoern Haeupl, Dominik C. Fuhrmann, Frank Wempe, Marcel Seibert, Sarah Weber, Antje Banning, Ritva Tikkanen, Richard Williams, Bernhard Bruene, Hubert Serve, Frank Schnuetgen, Ivana von Metzler, Nina Kurrle
Summary: The study analyzed the adaptation of multiple myeloma cells to hypoxia, revealing changes in protein expression and regulation of specific proteins under hypoxic conditions, including the cysteine protease LGMN, which can impact the growth of multiple myeloma cells in hypoxic environments.
Article
Hematology
Steffen Koschmieder, Susanne Isfort, Dominik Wolf, Florian H. Heidel, Andreas Hochhaus, Philippe Schafhausen, Martin Griesshammer, Denise Wolleschak, Uwe Platzbecker, Konstanze Doehner, Philipp J. Jost, Stefani Parmentier, Markus Schaich, Nikolas von Bubnoff, Frank Stegelmann, Angela Maurer, Martina Crysandt, Deniz Gezer, Maike Kortmann, Jeremy Franklin, Julia Frank, Martin Hellmich, Tim H. Bruemmendorf
Summary: This study found that treatment with ruxolitinib is effective, well-tolerated, and efficient for previously untreated patients with polycythemia vera, with significant reduction in symptoms and improvement in hematological parameters.
ANNALS OF HEMATOLOGY
(2023)
Article
Hematology
Jad Othman, Manja Meggendorfer, Enrico Tiacci, Christian Thiede, Richard Schlenk, Richard Dillon, Sebastian Stasik, Alessandra Venanzi, Sarah Bertoli, Eric Delabesse, Pierre-Yves Dumas, Arnaud Pigneux, Audrey Bidet, Amanda F. Gilkes, Ian Thomas, Maria Teresa Voso, Alessandro Rambaldi, Lorenzo Brunetti, Vincenzo M. Perriello, Vibeke Andresen, Bjorn T. Gjertsen, Maria Paola Martelli, Christian Recher, Christoph Roellig, Martin Bornhaeuser, Hubert Serve, Carsten Mueller-Tidow, Claudia D. Baldus, Tortsten Haferlach, Nigel Russell, Brunangelo Falini
Summary: The characteristics of therapy-related NPM1-mutated AML (t-NPM1 AML) were found to be similar to de novo NPM1-mutated AML (dn-NPM1 AML) in terms of genetics, transcriptional profile, and clinical outcomes. However, t-NPM1 AML showed better overall survival and relapse-free survival compared to t-AML.
Article
Hematology
Sebastian E. Koschade, Jan A. Stratmann, Bjoern Steffen, Shabnam Shaid, Fabian Finkelmeier, Hubert Serve, Wolfgang Miesbach, Christian H. Brandts, Olivier Ballo
Summary: This study investigated the incidence, risk factors, features, and outcomes of early-onset venous thromboembolic (VTE) events in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. The results showed that VTE occurred in 7.3% of the patients within 3 months of admission, with a median time to VTE of 3 days. Non-central venous catheter-related VTE was more common, and leukocytosis at admission was identified as an independent risk factor for VTE. The study suggests that early-onset VTE is a common complication in newly diagnosed AML patients, and further research is needed to understand the impact of non-CVC-related VTE on outcomes.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ahlam A. Ali, Lauren V. Cairns, Kathryn M. Clarke, Jaine K. Blayney, Katrina M. Lappin, Ken I. Mills
Summary: Paediatric acute myeloid leukaemia (AML) poses challenges in treatment, and there is no standard approach for young patients. Combination therapies that target multiple pathways could be a promising treatment option. Through in silico analysis, we identified cell death and survival as a potential target in paediatric AML and discovered novel drug combinations, such as ABT-737 + Purvalanol-A and ABT-737 + AKT inhibitor + SU9516, that showed significant synergism in AML cell lines. Our findings provide insights into potential combination treatments for AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marcelo A. S. de Toledo, Xuhuang Fu, Tiago Maie, Eva M. Buhl, Katrin Goetz, Susanne Schmitz, Anne Kaiser, Peter Boor, Till Braunschweig, Nicolas Chatain, Ivan G. Costa, Tim H. Bruemmendorf, Steffen Koschmieder, Martin Zenke
Summary: In this study, human induced pluripotent stem cells were differentiated into mast cells, which exhibited characteristics of systemic mastocytosis disease. These cells can be used for disease modeling and drug screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Oncology
Kirsi Manz, Jeanette Bahr, Till Ittermann, Konstanze Doehner, Steffen Koschmieder, Tim H. H. Bruemmendorf, Martin Griesshammer, Matthias Nauck, Henry Voelzke, Florian H. H. Heidel
Article
Hematology
Stuart Scott, Richard Dillon, Christian Thiede, Sadia Sadiq, Ashley Cartwright, Hazel J. Clouston, Debbie Travis, Katya Mokretar, Nicola Potter, Andrew Chantry, Liam Whitby
Summary: The European LeukaemiaNet (ELN) MRD working group has published guidelines for standardizing molecular genetic MRD testing of certain markers. A study involving 29 international laboratories showed that most participants were able to accurately detect and interpret MRD testing results, although some errors were identified. False-positive results were reported in the NPM1 marker-negative samples, emphasizing the need for ongoing quality assessment and proficiency testing. The study also highlighted the need for revising the guidelines to address interpretive issues and improve dissemination.
Article
Hematology
Maryam Ahmed S. Al Barashdi, Ahlam Ali, Mary Frances Mcmullin, Ken Mills
Summary: This study found that inhibition of CD45 could increase the sensitivity of cells to common chemotherapy drugs in myeloid malignancies, leading to improved treatment efficacy. Bioinformatics analysis also identified genes and drugs correlated with CD45 expression, which could serve as potential CD45 inhibitors. Therefore, CD45 inhibition may be a promising therapeutic approach for the treatment of myeloid malignancies.
ANNALS OF HEMATOLOGY
(2023)
Article
Hematology
Steffen Koschmieder, Susanne Isfort, Clemens Schulte, Lutz Jacobasch, Thomas Geer, Marcel Reiser, Michael Koenigsmann, Bernhard Heinrich, Jurgen Wehmeyer, Eyck von der Heyde, Hans Tesch, Benedikt Groeschl, Petra Bachhuber, Susanne Grosser, Heike L. Pahl
Summary: This study provides evidence for the safety and efficacy of ruxolitinib in elderly JAKi-naive patients with myelofibrosis in a real-world setting. The results show that ruxolitinib treatment leads to a reduction in spleen size and significant improvement in symptoms. Common adverse events include anemia and thrombocytopenia. Overall, ruxolitinib is a safe and effective treatment option for JAKi-naive patients with myelofibrosis.
ANNALS OF HEMATOLOGY
(2023)
Article
Medical Laboratory Technology
Wouter H. G. Hubens, Tiago Maie, Matthis Schnitker, Ledio Bocova, Deepika Puri, Martina Wessiepe, Jan Kramer, Lothar Rink, Steffen Koschmieder, Ivan G. Costa, Wolfgang Wagner
Summary: Cell-type specific DNA methylation can be used to accurately count different leukocyte subsets in blood. In this study, the authors developed targeted DNAm assays and used digital droplet PCR to measure DNAm levels in venous blood and dried blood samples. The results showed good correlations between epigenetic estimates and conventional cell counting methods, and dried blood samples facilitated self-sampling for easier testing accessibility.
CLINICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Fatemeh Mirzadeh Azad, Eduard A. Struys, Victoria Wingert, Luciana Hannibal, Ken Mills, Joop H. Jansen, Daniel B. Longley, Hendrik G. Stunnenberg, Yaser Atlasi
Summary: Understanding the mechanisms of epigenetic regulation in ESCs is crucial for stem cell and developmental biology. In this study, the identification of Spic as a marker of ground state pluripotency and its role in controlling 1C metabolism and histone marks highlight the importance of auxiliary TFs in linking cellular metabolism to epigenetic regulation in ESCs.
Editorial Material
Hematology
Madeline J. Caduc, Steffen Koschmieder
