Article
Oncology
Longlong Liu, Pradeep Kumar Patnana, Xiaoqing Xie, Daria Frank, Subbaiah Chary Nimmagadda, Annegret Rosemann, Marie Liebmann, Luisa Klotz, Bertram Opalka, Cyrus Khandanpour
Summary: This study demonstrates that AML cells with an MLL/AF9 genotype have a high dependency on oxidative phosphorylation and could be targeted for therapy using metformin.
Article
Oncology
Chengliang Yin, Junyan Zhang, Wei Guan, Liping Dou, Yuchen Liu, Ming Shen, Xiaodong Jia, Lu Xu, Rilige Wu, Yan Li
Summary: The study found that CLEC11A expression is higher in leukemia and high expression is associated with favorable prognosis. Methylation of CLEC11A is negatively correlated with its expression, with high methylation levels linked to poorer prognosis. CLEC11A is an up-regulated gene in leukemogenesis.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Kaylin G. Earnest, Erin M. McConnell, Eman M. Hassan, Mark Wunderlich, Bahareh Hosseinpour, Bianca S. Bono, Melissa J. Chee, James C. Mulloy, William G. Willmore, Maria C. DeRosa, Edward J. Merino
Summary: A DNA aptamer specific to AML cells was developed using SELEX technology in this study, showing specific binding to AML cells at a concentration of 37.5 nM, while displaying no binding to other cell types.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Sierrah M. Grigsby, Ann Friedman, Jennifer Chase, Bridget Waas, James Ropa, Justin Serio, Chenxi Shen, Andrew G. Muntean, Ivan Maillard, Zaneta Nikolovska-Coleska
Summary: The interaction between AF9 and DOT1L is crucial for MLL-driven leukemia cells but dispensable for non-leukemic hematopoiesis, suggesting a potential therapeutic strategy that selectively targets this interaction.
Article
Pharmacology & Pharmacy
Han Liu, Peng Chen, Yong-Long Yang, Ke-Wei Zhu, Tao Wang, Ling Tang, Yan-Ling Liu, Shan Cao, Gan Zhou, Hui Zeng, Xie-Lan Zhao, Wei Zhang, Xiao-Ping Chen
Summary: The study identified TBC1D16 as a potential predictor for chemosensitivity and prognosis in adult AML patients, with higher methylation and expression of this gene associated with increased risk of incomplete remission and worse overall survival.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Shuang-Hui Yang, Wei Liu, Jie Peng, Ya-Jing Xu, Yan-Feng Liu, Yan Li, Min-Yuan Peng, Zhao Ou-Yang, Cong Chen, En-Yi Liu
Summary: The study identified RhoBTB3 as a prognostic marker for non-M3 AML patients, aiding in treatment options selection between chemotherapy and allo-HCST. Allo-HSCT could improve prognosis in cases of RhoBTB3 downregulation, while high RhoBTB3 mRNA expression served as an independent favorable prognostic factor in chemotherapy patients.
Article
Oncology
Ana C. Vinado, Isabel A. Calvo, Itziar Cenzano, Danel Olaverri, Miguel Cocera, Patxi San Martin-Uriz, Juan P. Romero, Amaia Vilas-Zornoza, Laura Vera, Nuria Gomez-Cebrian, Leonor Puchades-Carrasco, Livia E. Lisi-Vega, Inigo Apaolaza, Pablo Valera, Elisabeth Guruceaga, Froilan Granero-Molto, Purificacion Ripalda-Cemborain, Tamara J. Luck, Lars Bullinger, Francisco J. Planes, Jose J. Rifon, Simon Mendez-Ferrer, Rushdia Z. Yusuf, Ana Pardo-Saganta, Felipe Prosper, Borja Saez
Summary: This study reveals that Prx1+ mesenchymal cells produce CXCL12 to maintain the survival of LSCs in the bone marrow of AML. Prx1+ cells promote LSC survival by modulating energy metabolism and the REDOX balance. Additionally, this phenomenon appears to be conserved in human patients.
Article
Cell & Tissue Engineering
Andrew Henry Lewis, Cory Seth Bridges, David Neal Moorshead, Taylor J. Chen, Wa Du, Barry Zorman, Pavel Sumazin, Monica Puppi, H. Daniel Lacorazza
Summary: In this study, we found that KLF4 plays an important role in acute myeloid leukemia (AML) and is related to the self-renewal and stemness of leukemia stem cells. Our experiments demonstrated that loss of KLF4 in leukemic granulocyte-macrophage progenitors (L-GMP) significantly reduced the frequency of leukemia stem cells and affected the cell cycle. We also found that upregulation of the DDX58 gene is associated with KLF4 loss and may be involved in this process. Therefore, KLF4 promotes leukemia progression in AML by regulating gene expression to support the division and stemness of leukemia stem cells.
Article
Biochemistry & Molecular Biology
Emanuela Chiarella, Annamaria Aloisio, Stefania Scicchitano, Katia Todoerti, Emanuela G. Cosentino, Daniela Lico, Antonino Neri, Nicola Amodio, Heather Mandy Bond, Maria Mesuraca
Summary: ZNF521 is implicated in sustaining self-renewal of immature AML cells by perturbing the gene expression landscape, ultimately favoring the expansion of MLL-AF9-transformed leukemic clones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Xiao-Na Zhu, Yu-Sheng Wei, Qian Yang, Hao-Ran Liu, Zhe Zhi, Di Zhu, Li Xia, Deng-Li Hong, Yun Yu, Guo-Qiang Chen
Summary: In this study, it was found that FBXO22 is highly expressed in MLLr AML and promotes AML progression by targeting BACH1 for degradation. Knockdown of FBXO22 leads to increased apoptosis in MLLr leukemia cells and reduced LSCs in serial transplantations. Targeting FBXO22 could be an ideal strategy to eradicate LSCs without affecting normal hematopoiesis.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Oncology
Chong Chen, Rong Wang, Wenli Feng, Feifei Yang, Lina Wang, Xiao Yang, Li Ren, Guoguang Zheng
Summary: The study revealed that the AML microenvironment impacted the kinetics and morphology of peritoneal resident macrophages, as well as significant differences in gene expression compared to normal macrophages. Additionally, the AML microenvironment affected the apoptosis, killing ability, and phagocytic function of peritoneal resident macrophages.
ANNALS OF TRANSLATIONAL MEDICINE
(2021)
Article
Hematology
Kai Zhang, Dingdong Liu, Yafei Li, Zhencan Shi, Jun Guo, Chengjiang Gao, Hu Wang, Zhenyu Ju, Daojun Diao
Summary: In this study, researchers discovered that the E3 ligase TRIM31 regulates HSC homeostasis and leukemia initiation by promoting the accumulation of CDK8. TRIM31 deficiency leads to increased proliferation of HSC and progenitor cells, as well as long-term HSC exhaustion. Additionally, TRIM31 deletion was found to accelerate the initiation of leukemia in a murine model of acute myeloid leukemia.
Article
Oncology
Jan Vorwerk, Kaiyan Sun, Daria Frank, Felix Neumann, Jana Hueve, Paulina Marie Budde, Longlong Liu, Xiaoqing Xie, Pradeep Kumar Patnana, Helal Mohammed Mohammed Ahmed, Bertram Opalka, Georg Lenz, Ashok Kumar Jayavelu, Cyrus Khandanpour
Summary: The GFI1-36N variant enhances proliferation of leukemic cells and could potentially serve as a marker for AML patients sensitive to CDK4/6 inhibitors.
FRONTIERS IN ONCOLOGY
(2022)
Article
Hematology
Wenli Feng, Xiao Yang, Lina Wang, Rong Wang, Feifei Yang, Hao Wang, Xiaoli Liu, Qian Ren, Yingchi Zhang, Xiaofan Zhu, Guoguang Zheng
Summary: High expression of P2X7 is correlated with worse survival outcomes in AML, especially in MLL-rearranged AML. P2X7 accelerates the progression of AML by promoting cell proliferation and increasing leukemia stem cells; P2X7 may contribute to leukemia and solid tumor progression through the P2X7-Pbx3 pathway.
Review
Medicine, Research & Experimental
Mengci Hu, Wenzhe Li, Youshan Zhang, Caixia Liang, Jie Tan, Ya Wang
Summary: Venetoclax, a potent BCL-2 inhibitor, has shown significant efficacy in AML treatment in preclinical and clinical trials. However, further research is needed to determine the optimal treatment strategies and identify biomarkers for predicting treatment response.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Oncology
Joanna Zaleska, Paulina Kwasnik, Magdalena Paziewska, Joanna Purkot, Aleksandra Szabelak, Mateusz Jurek, Natalia Masny, Izabela Dziatkiewicz, Bartosz Pronobis-Szczylik, Agnieszka Piebiak, Agnieszka Szymczyk, Katarzyna Jarosz-Chudzik, Lukasz Bolkun, Katarzyna Kozlowska, Jaroslaw Piszcz, Edyta Subocz, Janusz Halka, Michal Bator, Elzbieta Kalicinska, Tomasz Wrobel, Lidia Usnarska-Zubkiewicz, Justyna Rybka, Izabela Deren-Wagemann, Marta Szyca-Smieszniak, Jaroslaw Dybko, Iwona Hus, Bartosz Pula, Edyta Cichocka, Marcin Rymko, Dorota Zdunczyk, Mateusz Ziarkiewicz, Grzegorz Wladyslaw Basak, Lars Bullinger, Krzysztof Giannopoulos
Summary: Multiple myeloma and chronic lymphocytic leukemia patients have increased susceptibility to COVID-19 due to impaired immune function. This study evaluated the efficacy of mRNA COVID-19 vaccines in these patients and found that vaccination can induce specific CD8+ T cell responses, but they do not correlate positively with serological responses.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Hematology
Hideki Makishima, Ryunosuke Saiki, Yasuhito Nannya, Sophia Korotev, Carmelo Gurnari, June Takeda, Yukihide Momozawa, Steve Best, Pramila Krishnamurthy, Tetsuichi Yoshizato, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Yasunobu Nagata, Nobuyuki Kakiuchi, Makoto Onizuka, Kenichi Chiba, Hiroko Tanaka, Ayana Kon, Yotaro Ochi, Masahiro M. Nakagawa, Rurika Okuda, Takuto Mori, Akinori Yoda, Hidehiro Itonaga, Yasushi Miyazaki, Masashi Sanada, Takayuki Ishikawa, Shigeru Chiba, Hisashi Tsurumi, Senji Kasahara, Carsten Mueller-Tidow, Akifumi Takaori-Kondo, Kazuma Ohyashiki, Toru Kiguchi, Fumihiko Matsuda, Joop H. Jansen, Chantana Polprasert, Piers Blombery, Yoichiro Kamatani, Sator Miyano, Luca Malcovati, Torsten Haferlach, Michiaki Kubo, Mario Cazzola, Austin G. Kulasekararaj, Lucy A. Godley, Jaroslaw P. Maclejewski, Seishi Ogawa
Summary: DDX41 gene mutations play an important role in late-onset myeloid neoplasms, but many crucial features of DDX41-mutated neoplasms still need to be elucidated. This study comprehensively characterized DDX41-mutated neoplasms and found that DDX41 risk variants accounted for 80% of known genetic predispositions to myeloid neoplasms in adults. Additionally, DDX41 risk alleles were significantly enriched in Japanese cases and more prominent in males compared to females.
Article
Cardiac & Cardiovascular Systems
Canxia Shi, Joseph Pierre Aboumsallem, Navin Suthahar, Aniek O. de Graaf, Joop H. Jansen, Isabelle A. van Zeventer, Valentina Bracun, Sanne de Wit, Elles M. Screever, Pieter F. van den Berg, Wouter C. Meijers, Ron T. Gansevoort, Stephan J. L. Bakker, Pim van der Harst, Herman H. W. Sillje, Gerwin Huls, Rudolf A. de Boer
Summary: This study aimed to analyze the association between clonal hematopoiesis of indeterminate potential (CHIP) and incident heart failure (HF) in a European population cohort. Results showed that CHIP mutations were correlated with age, smoking, hypertension, and cardiovascular biomarkers, but the frequency of CHIP was similar between individuals with incident HF and control participants. However, among people younger than 65 years, CHIP mutations were more frequently detected in the case cohort and significantly associated with new-onset HF.
EUROPEAN JOURNAL OF HEART FAILURE
(2023)
Editorial Material
Medical Laboratory Technology
Erik-Jan Kamsteeg, Christian Gilissen
CLINICAL CHEMISTRY
(2023)
Article
Hematology
Elisa Donato, Nadia Correia, Carolin Andresen, Darja Karpova, Roberto Wuerth, Corinna Klein, Markus Sohn, Adriana Przybylla, Petra Zeisberger, Kathrin Rothfelder, Helmut Salih, Halvard Bonig, Sebastian Stasik, Christoph Roellig, Anna Dolnik, Lars Bullinger, Frank Buchholz, Christian Thiede, Daniel Huebschmann, Andreas Trumpp
Summary: This study proposes a novel flow cytometry sorting strategy for CD34 neg AML subtypes, enriching for leukemic stem cells (LSCs) independently of CD34 status by positive selection for GPR56 and negative selection for NKG2D ligands. The functional reconstitution capacity and transcriptomes of CD34- and CD34+ LSCs are shown to be similar, supporting the concept of phenotypic plasticity. Patients with AML who still retain functional hematopoietic stem cells (HSCs) at the time of diagnosis have longer relapse-free and overall survival.
Article
Oncology
Claudia M. Denkinger, Maike Janssen, Ulrike Schaekel, Julia Gall, Albrecht Leo, Patrick Stelmach, Stefan F. Weber, Johannes Krisam, Lukas Baumann, Jacek Stermann, Uta Merle, Markus A. Weigand, Christian Nusshag, Lars Bullinger, Jens-Florian Schrezenmeier, Martin Bornhaeuser, Nael Alakel, Oliver Witzke, Timo Wolf, Maria J. G. T. Vehreschild, Stefan Schmiedel, Marylyn M. Addo, Felix Herth, Michael Kreuter, Phil-Robin Tepasse, Bernd Hertenstein, Mathias Haenel, Anke Morgner, Michael Kiehl, Olaf Hopfer, Mohammad-Amen Wattad, Carl C. Schimanski, Cihan Celik, Thorsten Pohle, Matthias Ruhe, Winfried Kern, Anita Schmitt, Hanns-Martin Lorenz, Margarida Souto-Carneiro, Mary Gaeddert, Niels Halama, Stefan Meuer, Hans-Georg Kraeusslich, Barbara Mueller, Paul Schnitzler, Sylvia Parthe, Ralf Bartenschlager, Martina Gronkowski, Jennifer Klemmer, Michael Schmitt, Peter Dreger, Katharina Kriegsmann, Richard F. Schlenk, Carsten Muller-Tidow
Summary: Patients with cancer and compromised immune systems may benefit from convalescent/vaccinated plasma treatment to improve COVID-19 outcomes.
Article
Cardiac & Cardiovascular Systems
Alessia Lena, Ursula Wilkenshoff, Sara Hadzibegovic, Jan Porthun, Lukas Roesnick, Ann-Kathrin Froehlich, Tanja Zeller, Mahir Karakas, Ulrich Keller, Johann Ahn, Lars Bullinger, Hanno Riess, Stuart D. Rosen, Alexander R. Lyon, Thomas F. Luescher, Matthias Totzeck, Tienush Rassaf, Daniel Burkhoff, Mandeep R. Mehra, Jeroen J. Bax, Javed Butler, Frank Edelmann, Wilhelm Haverkamp, Stefan D. Anker, Milton Packer, Andrew J. S. Coats, Stephan von Haehling, Ulf Landmesser, Markus S. Anker
Summary: This study found that cancer patients have cardiac wasting and decreased heart function. Low left ventricular mass is associated with poor functional status and increased all-cause mortality in cancer patients.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Article
Oncology
Jana K. Striefler, Phung T. Binder, Franziska Brandes, Daniel Rau, Silvan Wittenberg, David Kaul, Siyer Roohani, Armin Jarosch, Frederik M. Schaefer, Robert Oellinger, Sven Maerdian, Lars Bullinger, Kai -Uwe Eckardt, Jan Kruse, Anne Floercken
Summary: This study retrospectively analyzed sarcoma patients admitted to the ICU from 2005 to 2022. Sex, tumor localization, therapeutic intention, line of chemotherapy, SAPS II score, and SOFA score significantly impacted overall survival. The study confirms the predictive relevance of established sepsis and performance scores in sarcoma patients.
CANCER MANAGEMENT AND RESEARCH
(2023)
Letter
Hematology
Charlotte C. M. Schaap, Saskia E. M. Schols, Frank W. M. B. Preijers, Emiel de Jonge, Coby M. M. Laarakkers, Joop H. Jansen, Nicole M. A. Blijlevens, Dorine W. Swinkels, Saskia M. C. Langemeijer
Article
Oncology
P. K. J. D. de Jonge, P. M. M. van Hauten, L. D. Janssen, A. L. de Goede, M. M. Berrien-Elliott, J. M. R. van der Meer, C. M. Mousset, M. W. H. Roeven, M. Foster, N. Blijlevens, W. Hobo, T. A. Fehniger, J. H. Jansen, N. P. M. Schaap, H. Dolstra
Summary: Allogeneic natural killer (NK) cell-based immunotherapy is a promising approach for acute myeloid leukemia (AML). A good manufacturing practice (GMP)-compliant, cytokine-based ex vivo manufacturing process for generating NK cells from CD34(+) hematopoietic stem and progenitor cells (HSPC) has been developed. This process generates a consistent and active NK cell product that meets the requirements for NK cell immunotherapy. The manufactured NK cell batches are used in a clinical trial approved by the Dutch Ethics Committee.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Jesper van Eck van der Sluijs, Diede van Ens, Jolanda Brummelman, Daan Heister, Aastha Sareen, Lisa Truijen, Dorette S. van Ingen Schenau, Mirjam H. M. Heemskerk, Marieke Griffioen, Michel G. D. Kester, Nicolaas P. M. Schaap, Joop H. Jansen, Anniek B. van der Waart, Harry Dolstra, Willemijn Hobo
Summary: Non-DCs have been found to enhance the activation and expansion of antigen-specific CD8+ T cells mediated by DCs, without impairing the NK cell responses in vitro and in vivo. This provides a rationale for further clinical translation of the CD34+-derived DC-complete vaccine in hemato-oncology patients post alloSCT.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Markus S. Anker, Sophia K. Potthoff, Alessia Lena, Jan Porthun, Sara Hadzibegovic, Ruben Evertz, Corinna Denecke, Ann-Kathrin Froehlich, Frederike Sonntag, Vera Regitz-Zagrosek, Stuart D. Rosen, Alexander R. Lyon, Thomas F. Luescher, John A. Spertus, Stefan D. Anker, Mahir Karakas, Lars Bullinger, Ulrich Keller, Ulf Landmesser, Javed Butler, Stephan von Haehling
Summary: This study compared the EORTC QLQ-C30 and ESC HeartQoL questionnaires for assessing health-related quality of life in cancer patients, and found that both instruments were associated with increased mortality in cancer patients. Combining both questionnaires provided even greater stratification of patient risk.
EUROPEAN JOURNAL OF HEART FAILURE
(2023)
Article
Genetics & Heredity
Rabia Basharat, Kim Rodenburg, Maria Rodriguez-Hidalgo, Afeefa Jarral, Ehsan Ullah, Jordi Corominas, Christian Gilissen, Syeda Tatheer Zehra, Usman Hameed, Muhammad Ansar, Suzanne E. de Bruijn
Summary: This study performed genome sequencing on families affected by anophthalmia and microphthalmia, and identified known and novel genetic variants associated with these disorders. The findings highlight the importance of genome sequencing for accurate diagnosis and the role of non-coding variants in these eye disorders.
Article
Multidisciplinary Sciences
Kai Rejeski, Ariel Perez, Gloria Iacoboni, Viktoria Blumenberg, Veit L. Buecklein, Simon Voelkl, Olaf Penack, Omar Albanyan, Sophia Stock, Fabian Mueller, Philipp Karschnia, Agnese Petrera, Kayla Reid, Rawan Faramand, Marco L. Davila, Karnav Modi, Erin A. Dean, Christina Bachmeier, Michael von Bergwelt-Baildon, Frederick L. Locke, Wolfgang Bethge, Lars Bullinger, Andreas Mackensen, Pere Barba, Michael D. Jain, Marion Subklewe
Summary: Study reveals that intermittent neutrophil recovery after CAR-T cell therapy is associated with better survival outcomes, while aplastic recovery is associated with unfavorable expansion and tumor burden. Serum proteomics analysis shows that prolonged neutrophil aplasia occurs in patients with baseline systemic immune dysregulation, characterized by markers of endothelial dysfunction, increased inflammatory cytokines, macrophage activation, and T cell suppression. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion.
Article
Hematology
Marius-Konstantin Klever, Eric Straeng, Sara Hetzel, Julius Jungnitsch, Anna Dolnik, Robert Schoepffin, Jens-Florian Schrezenmeier, Felix Schick, Olga Blau, Joerg Westermann, Frank G. Ruecker, Zuyao Xia, Konstanze Doehner, Hubert Schrezenmeier, Malte Spielmann, Alexander Meissner, Uira Souto Melo, Stefan Mundlos, Lars Bullinger
Summary: CK-AML is associated with poor prognosis, partly explained by TP53 mutations and complex chromosomal rearrangements. A novel phenomenon called "chromocataclysm" has been discovered, revealing extreme density of structural variants in CK-AML patients, which could have implications for identifying important drivers underlying cancer with complex karyotypic changes.