Article
Medicine, Research & Experimental
Xue-Ping Li, Wei-Na Zhang, Jia-Ying Mao, Bai-Tian Zhao, Lu Jiang, Yan Gao
Summary: In this study, we constructed a CD34(+)CD117(dim) population signature model for predicting clinical outcome of AML patients using gene expression and RNA-seq data. The high-risk group exhibited worse overall survival and had activated immune signaling pathways. This model may serve as a valuable tool for stratifying AML patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Editorial Material
Cell & Tissue Engineering
Malini Gupta, Britta Will
Summary: Adaptive aberrant gene regulation is a hallmark of malignant growth and therapy resistance in acute myeloid leukemia (AML). In this study, Eagle et al. identified oncogenic enhancer-driven overexpression of selenophosphate synthetase 2 (SEPHS2) as a targeted opportunity for mitigating malignant cell growth in AML.
Article
Cell & Tissue Engineering
Paul Jaeger, Stefanie Geyh, Soeren Twarock, Ron-Patrick Cadeddu, Pablo Rabes, Annemarie Koch, Uwe Maus, Tobias Hesper, Christoph Zilkens, Christina Rautenberg, Felix Bormann, Karl Koehrer, Patrick Petzsch, Dagmar Wieczorek, Beate Betz, Harald Surowy, Barbara Hildebrandt, Ulrich Germing, Guido Kobbe, Rainer Haas, Thomas Schroeder
Summary: Studies suggest that leukemic cells induce functional inhibition of healthy CD34+ HSPC, at least in part, through pathways like TGF beta 1, indicating that blocking this pathway may improve hematopoiesis in AML patients.
Review
Biochemistry & Molecular Biology
Daniela Damiani, Mario Tiribelli
Summary: The prognosis of acute myeloid leukemia (AML) is poor due to tumor cell immune escape, which weakens T-cells. Inhibiting immune checkpoints (ICs) through immune checkpoint inhibitors (ICIs) has emerged as a promising therapeutic strategy for AML. However, the results of clinical trials testing ICIs, alone or in combination with other treatments, in AML are conflicting.
Review
Biochemistry & Molecular Biology
Vijendra Singh, Mohammed Hafiz Uddin, Jeffrey A. Zonder, Asfar S. Azmi, Suresh Kumar Balasubramanian
Summary: While mechanistic studies have shed light on the molecular mechanisms of AML and led to the development of new targeted therapies, resistance remains a significant issue in AML treatment. The exploration of circRNA in AML biology and therapy resistance shows promise in providing new insights and potential solutions to managing this disease.
Review
Biochemistry & Molecular Biology
Rikako Tabata, SungGi Chi, Junichiro Yuda, Yosuke Minami
Summary: Studies have suggested the potential clinical benefits of immuno-oncology therapy against AML, including immune checkpoint inhibitors and bi-/tri-specific antibodies. CAR-T and NK cells have shown effectiveness for relapsed/refractory AML patients, and conventional chemotherapy combined with anti-PD-1/anti-CTLA4 antibodies also demonstrated certain efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Fenghua Qian, Brooke E. Arner, Kathleen M. Kelly, Charyguly Annageldiyev, Arati Sharma, David F. Claxton, Robert F. Paulson, K. Sandeep Prabhu
Summary: Interleukin-4 (IL-4) plays a therapeutic role in acute myeloid leukemia (AML) by alleviating the severity of the disease. IL-4 enhances the expression of hematopoietic- PGD(2) synthase (H-PGDS) to increase the production of endogenous cyclopentenone prostaglandins (CyPGs), leading to apoptosis of leukemia-initiating cells (LICs).
Review
Chemistry, Medicinal
Vincent G. Sorrentino, Srijan Thota, Edward A. Gonzalez, Pranela Rameshwar, Victor T. Chang, Jean-Pierre Etchegaray
Summary: Myelodysplastic Syndromes (MDS) affecting the elderly can progress to Acute Myeloid Leukemia (AML), with epigenetic alterations such as DNA methylation and chromatin modification playing a role in their initiation and progression. DNA hypomethylating agents like decitabine and azacitidine have shown efficacy in treating hematological malignancies, while the proteasome inhibitor bortezomib is used in multiple myeloma (MM) chemotherapy. Phase III clinical trials have demonstrated the potential of these drugs in prolonging survival and treating MDS and AML, although further research is needed to fully understand their mechanisms and effects.
Review
Oncology
Kristen J. Kurtz, Shannon E. Conneely, Madeleine O'Keefe, Katharina Wohlan, Rachel E. Rau
Summary: Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous hematologic malignancy. Murine models of AML are indispensable research tools to better understand the mechanisms and test novel therapeutic approaches for this disease.
FRONTIERS IN ONCOLOGY
(2022)
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
Chengtao Zhang, Da Gao, Xiaohong Wang, Xiuli Sun, Yan Yan, Yan Yang, Jingjing Zhang, Jinsong Yan
Summary: This study investigated the effectiveness and safety of a new induction therapy (BHA) for patients with refractory/relapsed acute myeloid leukemia (R/R AML). The results showed a CR/CRi rate of 38.1% after one course of BHA and a higher CR/CRi rate of 66.7% in patients with FLT3 mutation. BHA chemotherapy regimen was found to be safe and tolerable for R/R AML patients, especially those with FLT3 mutation.
FRONTIERS IN ONCOLOGY
(2023)
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)
Article
Medicine, General & Internal
Pau Montesinos, Christian Recher, Susana Vives, Ewa Zarzycka, Jianxiang Wang, Giambattista Bertani, Michael Heuser, Rodrigo T. Calado, Andre C. Schuh, Su-Peng Yeh, Scott R. Daigle, Jianan Hui, Shuchi S. Pandya, Diego A. Gianolio, Stephane de Botton, Hartmut Dohner
Summary: This study demonstrated that the combination therapy of oral ivosidenib and azacitidine showed better event-free survival and longer overall survival in patients with newly diagnosed IDH1-mutated acute myeloid leukemia.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Medicine, General & Internal
Laura F. Newell, Rachel J. Cook
Summary: AML, a rare and potentially catastrophic diagnosis, has seen recent advancements in personalized therapy and novel treatment options due to discoveries of molecular drivers of the disease.
BMJ-BRITISH MEDICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Bing Long, Yongli Shan, Yanling Sun, Tianyu Wang, Xudong Li, Ke Huang, Wenwen Zhang, Yi He, Ruijuan Wen, Yuhang Li, Yuchan Mai, Yashu Feng, Tian Zhang, Baoqiang Kang, Cong Zhang, Yanling Zhu, Jiaming Gu, Jiajun Liu, Xiangzhong Zhang, Guangjin Pan
Summary: Vitamin C significantly enhances the therapeutic effect of DZNep on leukemia cells, reducing drug resistance.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Medical Laboratory Technology
Orianne Wagner-Ballon, Peter Bettelheim, Jeroen Lauf, Frauke Bellos, Matteo Della Porta, Erica Travaglino, Dolores Subira, Irene Nuevo Lopez, Sihem Tarfi, Theresia M. Westers, Ulrika Johansson, Katherina Psarra, Serafeim Karathanos, Sergio Matarraz, Enrique Colado, Monali Gupta, Robin Ireland, Wolfgang Kern, Arjan A. Van de Loosdrecht
Summary: This multicenter study demonstrates the robustness of the monocyte assay in distinguishing chronic myelomonocytic leukemia from other causes of monocytosis. It also confirms the possibility of using this assay in bone marrow samples.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Oncology
Meletios A. Dimopoulos, Dominik Dytfeld, Sebastian Grosicki, Philippe Moreau, Naoki Takezako, Mitsuo Hori, Xavier Leleu, Richard LeBlanc, Kenshi Suzuki, Marc S. Raab, Paul G. Richardson, Mihaela Popa McKiver, Ying-Ming Jou, David Yao, Prianka Das, Jesus San-Miguel
Summary: In the phase II ELOQUENT-3 trial, the combination of Elotuzumab, Pomalidomide, and Dexamethasone (EPd) showed significant improvement in progression-free survival (PFS) compared to Pomalidomide and Dexamethasone (Pd) in relapsed/refractory multiple myeloma patients previously treated with Lenalidomide and a proteasome inhibitor. The final overall survival (OS) results revealed that EPd had a statistically significant improvement in OS.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Adam D. Cohen, Maria-Victoria Mateos, Yael C. Cohen, Paula Rodriguez-Otero, Bruno Paiva, Niels W. C. J. van de Donk, Thomas Martin, Attaya Suvannasankha, Kevin C. De Braganca, Christina Corsale, Jordan M. Schecter, Helen Varsos, William Deraedt, Liwei Wang, Martin Vogel, Tito Roccia, Xiaoying Xu, Pankaj Mistry, Enrique Zudaire, Muhammad Akram, Tonia Nesheiwat, Lida Pacaud, Irit Avivi, Jesus San-Miguel
Summary: The CARTITUDE-2 study evaluated the safety and efficacy of cilta-cel in patients with multiple myeloma who had previously received anti-BCMA treatment. The results showed that cilta-cel induced favorable responses in patients who had exhausted other therapies.
Article
Oncology
Fredrik Schjesvold, Bruno Paiva, Vincent Ribrag, Paula Rodriguez-Otero, Jesus F. San-Miguel, Pawel Robak, Markus Hansson, Maika Onishi, Habib Hamidi, Vikram Malhi, Monique Dail, Apurva Javery, Grace Ku, Marc S. Raab
Summary: This phase Ib/II trial evaluated the safety and efficacy of cobimetinib alone and in combination with venetoclax, with or without atezolizumab in patients with relapsed/refractory multiple myeloma. The results showed that cobimetinib alone and in combination with venetoclax, with or without atezolizumab, was safe and tolerable, with moderate anti-tumor activity overall, and higher activity in patients with translocation t(11;14).
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Oncology
Maria Victoria Mateos, Felipe Prosper, Jesus Martin Sanchez, Enrique M. Ocio, Albert Oriol, Cristina Motllo, Jean-Marie Michot, Isidro Jarque, Rebeca Iglesias, Maria Sole, Sara Martinez, Carmen Kahatt, Salvador Fudio, Gema Corral, Ali Zeaiter, Lola Montilla, Vincent Ribrag
Summary: The triple combination of plitidepsin, BTZ, and DXM showed moderate activity and acceptable safety in adult patients with relapsed/refractory multiple myeloma.
Editorial Material
Oncology
Jens Hillengass, Tom Martin, Noemi Puig, Bruno Paiva, Saad Usmani, Shaji Kumar, Jesus San-Miguel
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Oncology
Meletios A. Dimopoulos, Albert Oriol, Hareth Nahi, Jesus San-Miguel, Nizar J. Bahlis, Saad Z. Usmani, Neil Rabin, Robert Z. Orlowski, Kenshi Suzuki, Torben Plesner, Sung-Soo Yoon, Dina Ben Yehuda, Paul G. Richardson, Hartmut Goldschmidt, Donna Reece, Tahamtan Ahmadi, Xiang Qin, Wendy Garvin Mayo, Xue Gai, Jodi Carey, Robin Carson, Philippe Moreau
Summary: Based on the analysis of POLLUX, daratumumab in combination with lenalidomide and dexamethasone significantly prolonged progression-free survival in patients with relapsed or refractory multiple myeloma. The final analysis also showed that this combination therapy improved overall survival in these patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Oncology
Meletios A. Dimopoulos, Jesus San-Miguel
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Enrique M. Ocio, Aurore Perrot, Pierre Bories, Jesus F. San-Miguel, Igor W. Blau, Lionel Karlin, Joaquin Martinez-Lopez, Song-Yau Wang, Sara Bringhen, Magda Marcatti, Maria-Victoria Mateos, Paula Rodriguez-Otero, Stefania Oliva, Axel Nogai, Nadia Le Roux, Liyan Dong, Sandrine Mace, Matthieu Gassiot, Thomas Fitzmaurice, Corina Oprea, Philippe Moreau
Summary: This study evaluated the preliminary efficacy, safety, and pharmacokinetics of Isatuximab combined with bortezomib-lenalidomide-dexamethasone in patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation. The results showed a high overall response rate and minimal residual disease negativity, indicating the potential advantages of Isatuximab in this patient population.
Article
Biochemistry & Molecular Biology
Marta Larrayoz, Maria J. Garcia-Barchino, Jon Celay, Amaia Etxebeste, Maddalen Jimenez, Cristina Perez, Raquel Ordonez, Cesar Cobaleda, Cirino Botta, Vicente Fresquet, Sergio Roa, Ibai Goicoechea, Catarina Maia, Miren Lasaga, Marta Chesi, P. Leif Bergsagel, Maria J. Larrayoz, Maria J. Calasanz, Elena Campos-Sanchez, Jorge Martinez-Cano, Carlos Panizo, Paula Rodriguez-Otero, Silvestre Vicent, Giovanna Roncador, Patricia Gonzalez, Satoru Takahashi, Samuel G. Katz, Loren D. Walensky, Shannon M. Ruppert, Elisabeth A. Lasater, Maria Amann, Teresa Lozano, Diana Llopiz, Pablo Sarobe, Juan J. Lasarte, Nuria Planell, David Gomez-Cabrero, Olga Kudryashova, Anna Kurilovich, Maria V. Revuelta, Leandro Cerchietti, Xabier Agirre, Jesus San Miguel, Bruno Paiva, Felipe Prosper, Jose A. Martinez-Climent
Summary: The lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) has hindered therapeutic discoveries. To overcome this limitation, researchers used genetically engineered mice to develop bone marrow tumors that mimic MM pathogenesis. Integrative analyses of mice and patients revealed a common genetic pathway that accelerates disease progression and immune evasion mechanisms that remodel the bone marrow microenvironment differently.
Article
Medicine, General & Internal
Jesus San-Miguel, Binod Dhakal, Kwee Yong, Andrew Spencer, Sebastien Anguille, Maria-Victoria Mateos, Carlos Fernandez de Larrea, Joaquin Martinez-Lopez, Philippe Moreau, Cyrille Touzeau, Xavier Leleu, Irit Avivi, Michele Cavo, Tadao Ishida, Seok Jin Kim, Wilfried Roeloffzen, Niels W. C. J. van de Donk, Dominik Dytfeld, Surbhi Sidana, Luciano J. Costa, Albert Oriol, Rakesh Popat, Abdullah M. Khan, Yael C. Cohen, P. Joy Ho, James Griffin, Nikoletta Lendvai, Carolina Lonardi, Ana Slaughter, Jordan M. Schecter, Carolyn C. Jackson, Kaitlyn Connors, Katherine Li, Enrique Zudaire, Diana Chen, Jane Gilbert, T. Yeh, Sarah Nagle, Erika Florendo, Lida Pacaud, Nitin Patel, Simon J. Harrison, Hermann Einsele
Summary: In patients with lenalidomide-refractory multiple myeloma, Ciltacabtagene autoleucel (CAR-T cell therapy) showed a lower risk of disease progression or death compared to standard care, highlighting its effectiveness in this patient population.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Teresa Caballero-Velazquez, Olga Perez-Lopez, Ana Yeguas Bermejo, Eduardo Rodriguez Arboli, Enrique Colado Varela, Amparo Sempere Talens, Maria Belen Vidriales, Maria Sole-Rodriguez, Covadonga Quiros Caso, Estefania Perez Lopez, Marta Reinoso Segura, Concepcion Prats-Martin, Pau Montesinos, Jose A. Perez-Simon
Summary: This study aimed to evaluate the prognostic value of measurable residual disease (MRD) in AML patients undergoing hematopoietic stem cell transplantation (HSCT). MRD detection before and after transplantation has prognostic value, and positive MRD on day +100 after transplantation is associated with a poor prognosis. Standardized MRD testing can predict the outcome of AML patients in real life.
Article
Hematology
Katja Weisel, Meletios A. Dimopoulos, Jesus San-Miguel, Agne Paner, Monika Engelhardt, Fiona Taylor, Jennifer Lord-Bessen, Christine Yip, Mike Greenwood, Jackson Tang, Michele Cavo
Summary: Triplet regimens with immunomodulatory drugs and proteasome inhibitors have improved outcomes for patients with relapsed/refractory multiple myeloma. In the ELOQUENT-3 trial, the addition of elotuzumab to pomalidomide and dexamethasone did not impact the health-related quality of life (HRQoL) of patients. HRQoL remained stable and there were no significant differences between the treatment arms.
Article
Biochemistry & Molecular Biology
Elena Spinola-Lasso, Juan Carlos Montero, Roberto Jimenez-Monzon, Francisco Estevez, Jose Quintana, Borja Guerra, Khaled M. Elokely, Francisco Leon, Henoc del Rosario, Leandro Fernandez-Perez, Manuel Rodriguez Lopez, Bonifacio Nicolas Diaz-Chico, Grant McNaughton-Smith, Atanasio Pandiella, Juan Carlos Diaz-Chico
Summary: In this study, a novel compound CM728 with a quinone-fused oxazepine structure was found to exhibit potent antitumor effects against triple-negative breast cancer (TNBC). CM728 inhibited TNBC cell viability and decreased tumor growth in vivo. It also showed a synergistic antiproliferative effect with docetaxel. Mechanistically, CM728 bound to peroxiredoxin-1 (Prdx1), inducing its oxidation and activating JNK/p38 MAPK and inhibiting STAT3. CM728 also induced DNA damage, cell cycle arrest, and caspase-dependent apoptosis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)