Article
Hematology
Matteo Grioni, Arianna Brevi, Elena Cattaneo, Alessandra Rovida, Jessica Bordini, Maria Teresa Sabrina Bertilaccio, Maurilio Ponzoni, Giulia Casorati, Paolo Dellabona, Paolo Ghia, Matteo Bellone, Arianna Calcinotto
Summary: The presence of CD4(+) T cells is essential for the development of chronic lymphocytic leukemia (CLL), while CD8(+) T cells have an antitumor effect in restraining CLL progression. Antigen specificity of CD4(+) T cells has marginal impact on CLL development.
Article
Oncology
Selcen Ozturk, Verena Kalter, Philipp M. Roessner, Murat Sunbul, Martina Seiffert
Summary: The tryptophan-catabolizing enzyme IDO1 and its metabolite kynurenine were found to be enhanced in chronic lymphocytic leukemia (CLL) patients, potentially contributing to T cell suppression and immune escape. However, despite the upregulation of IDO1 in CLL, its inhibition appears insufficient to control leukemia development.
Article
Oncology
Maria Schubert, Franz Josef Gassner, Michael Huemer, Jan Philip Hoepner, Ekaterina Akimova, Markus Steiner, Alexander Egle, Richard Greil, Nadja Zaborsky, Roland Geisberger
Summary: The study demonstrates that AID contributes to the acquisition of somatic cancer-specific mutations in chronic lymphocytic leukemia, leading to accelerated disease progression and affecting the survival rate of mice. Therefore, further research on the impact of AID inhibition on drug resistance development is crucial.
Article
Hematology
Bola S. Hanna, Haniyeh Yazdanparast, Yasmin Demerdash, Philipp M. Roessner, Ralph Schulz, Peter Lichter, Stephan Stilgenbauer, Martina Seiffert
Summary: Ibrutinib, as a BTK inhibitor, not only affects CLL cells by blocking B-cell receptor signaling, but also impacts the microenvironment and CD8(+) T cells. Direct effects on TCR activity and the potential for co-stimulation via CD28 to overcome these effects have been demonstrated in studies. Additionally, combination therapy with PD-1/PD-L1 blockade shows promise in improving CD8(+) T-cell function in CLL.
Article
Hematology
Arnon P. Kater, Erik Slinger, Gaspard Cretenet, Anne W. Martens, Sriram Balasubramanian, Joel D. Leverson, Eric Eldering
Summary: In a mouse model study, combination therapy using ibrutinib and venetoclax showed deeper treatment effects on chronic lymphocytic leukemia (CLL), mainly due to reduced proliferation and increased apoptosis. Changes in T-cell subsets were most pronounced after combination treatment, which outperformed single-agent therapy.
Article
Oncology
Susanne Gonder, Anne Largeot, Ernesto Gargiulo, Sandrine Pierson, Iria Fernandez Botana, Giulia Pagano, Jerome Paggetti, Etienne Moussay
Summary: In this study, new transgenic murine conditional knock-out models of CLL were generated to investigate the role of the transcription factors HIF-1 alpha and AHR. Surprisingly, it was observed that both factors are dispensable for leukemia development in these models.
Article
Pharmacology & Pharmacy
Francesca Vanni, Ludovica Lopresti, Vanessa Zurli, Anna Kabanova, Francesca Cattaneo, Anna Sicuranza, Alessandro Gozzetti, Sandra Gemma, Daniela M. Zisterer, Monica Bocchia, Giuseppe Campiani, Cosima T. Baldari, Stefania Butini, Cristina Ulivieri
Summary: The study demonstrates that the novel compound OBC-1 restores p66Shc expression, promotes apoptosis, and prolongs survival in patients with chronic lymphocytic leukemia. By activating the JNK/STAT4 pathway, OBC compounds not only affect the behavior of leukemia cells but also have dual therapeutic effects of mobilizing cells from the spleen and inducing apoptosis in circulating leukemia cells.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Medicine, General & Internal
Alessandro Broccoli, Lisa Argnani, Alice Morigi, Laura Nanni, Beatrice Casadei, Cinzia Pellegrini, Vittorio Stefoni, Pier Luigi Zinzani
Summary: Ibrutinib has shown significant clinical impact in treating patients with chronic lymphocytic leukemia, including those with unfavorable cytogenetics and molecular markers. The drug is effective and well tolerated, with durable responses and a favorable safety profile in real-life settings. Adverse reactions mainly include hematological and extrahematological toxicities.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Hematology
Burcu Aslan, Gorkem Kismali, Lisa S. Chen, LaKesla R. Iles, Mikhila Mahendra, Michael Peoples, Mihai Gagea, Natalie W. Fowlkes, Xiaofeng Zheng, Jing Wang, Christopher P. Vellano, Joseph R. Marszalek, Maria Teresa Sabrina Bertilaccio, Varsha Gandhi
Summary: Research established cell lines overexpressing wild-type or mutant BTK to study the impact on signaling pathways, cell cycle, and molecular profiles. Xenograft mouse models were also created to mimic ibrutinib-resistant CLL, providing a tool for testing new therapeutic strategies.
Article
Oncology
Seval Akpinar, Mehmet Hilmi Dogu, Serhat Celik, Omer Ekinci, Ipek Yonal Hindilerden, Mehmet Sinan Dal, Eren Arslan Davulcu, Atakan Tekinalp, Fehmi Hindilerden, Busra Gokce Ozcan, Tuba Hacibekiroglu, Mehmet Ali Erkurt, Metin Bagci, Sinem Namdaroglu, Gulten Korkmaz, Oktay Bilgir, Gulsum Akgun Cagliyan, Hacer Berna Afacan Ozturk, Istemi Serin, Tarik Onur Tiryaki, Duzgun Ozatli, Serdal Korkmaz, Turgay Ulas, Bulent Eser, Burhan Turgut, Fevzi Altuntas
Summary: In this study, we evaluated the safety and efficacy of single-agent ibrutinib for relapsed/refractory CLL in real-world settings. The results demonstrated good safety and efficacy, with a median overall survival of 52 months.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Letter
Oncology
Jayna J. Mistry, Charlotte Hellmich, Amelia Lambert, Jamie A. Moore, Aisha Jibril, Angela Collins, Kristian M. Bowles, Stuart A. Rushworth
Summary: Despite recent advances in treatment, acute myeloid leukemia (AML) remains an incurable malignancy. However, the combination treatment of Venetoclax and Daratumumab may potentially slow tumor progression and reduce leukemia growth in both in vitro and in vivo settings, providing evidence for clinical evaluation.
BIOMARKER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Huaixiao Ma, Yuqi Ning, Lin Wang, Weidao Zhang, Ping Zheng
Summary: Maintaining genomic stability is crucial for embryonic stem cells (ESCs). ESCs eliminate unrepaired DNA damage through differentiation and apoptosis, with tumor suppressor p53 known to be involved in this process. This study identified a p53-independent quality control factor called lncRNA NONMMUT028956 (Lnc956) in mouse ESCs. Lnc956 is abundantly expressed in ESCs and regulates ESC differentiation after DNA damage, promoting interaction with Kruppel-like factor 4 (KLF4). This interaction sequesters KLF4 and prevents its transcriptional regulation on pluripotency, favoring the shutdown of pluripotency regulatory circuitry. Additionally, ATM signaling in ESCs activates both the p53 and Lnc956 pathways to ensure robust differentiation and apoptosis in response to unrepaired DNA damage.
Article
Multidisciplinary Sciences
Seyed Pairawan, Argun Akcakanat, Scott Kopetz, Coya Tapia, Xiaofeng Zheng, Huiqin Chen, Min Jin Ha, Yasmeen Rizvi, Vijaykumar Holla, Jing Wang, Kurt W. Evans, Ming Zhao, Naifa Busaidy, Bingliang Fang, Jack A. Roth, Ecaterina Ileana Dumbrava, Funda Meric-Bernstam
Summary: Combination therapy with MEK inhibitor selumetinib and MDM2 inhibitor KRT-232 was evaluated in colon and thyroid cancer models. The study showed that the combination therapy had better antitumor efficacy than single drug therapy in both in vitro and in vivo settings.
SCIENTIFIC REPORTS
(2022)
Article
Nutrition & Dietetics
Shusuke Iwata, Ryusuke Yoshida, Shingo Takai, Keisuke Sanematsu, Noriatsu Shigemura, Yuzo Ninomiya
Summary: This study found that adrenomedullin enhances sugar sensing in mouse taste cells, potentially impacting caloric sensing and food intake.
Article
Gastroenterology & Hepatology
Cong Xu, Jieqing Fan, Danyang Liu, Aimaier Tuerdi, Juanjuan Chen, Yuning Wei, Yanfang Pan, Huaixin Dang, Xiong Wei, Ashraf Siddig Yousif, Jeysen Yogaratnam, Qiong Zhou, Henri Lichenstein, Tian Xu
Summary: The study demonstrates that DF-006 exhibits antiviral efficacy against HBV in mouse and PHH models without overt toxicity. In mice, DF-006 primarily targets the liver and activates innate immunity to mediate its anti-HBV effects.
Article
Oncology
Miguel Gallardo, Prerna Malaney, Marisa J. L. Aitken, Xiaorui Zhang, Todd M. Link, Vrutant Shah, Sanzhar Alybayev, Meng-Han Wu, Laura R. Pageon, Huaxian Ma, Rodrigo Jacamo, Li Yu, Zijun Y. Xu-Monette, Haley Steinman, Hun Ju Lee, Dos Sarbassov, Inmaculada Rapado, Michelle C. Barton, Joaquin Martinez-Lopez, Carlos Bueso-Ramos, Ken H. Young, Sean M. Post
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2020)
Article
Hematology
Marisa J. L. Aitken, Christopher B. Benton, Wang Feng, Zhang Jianhua, Shelley M. Herbrich, Koichi Takahashi, Carlos E. Bueso-Ramos, Nicholas J. Short
AMERICAN JOURNAL OF HEMATOLOGY
(2020)
Article
Hematology
Esther Onecha, Inmaculada Rapado, Maria Luz Morales, Gonzalo Carreno-Tarragona, Pilar Martinez-Sanchez, Xabier Gutierrez, Jose Maria Sanchez Pina, Maria Linares, Miguel Gallardo, Joaquin Martinez-Lopez, Rosa Ayala
Summary: In cases of treatment failure in acute myeloid leukemia (AML), mutational profiling can help differentiate primary refractoriness from relapse, providing insights for treatment guidance and prognostic risk assessment. Additionally, molecular follow-up using a custom NGS myeloid panel can aid in monitoring treatment response, identifying minimal residual disease markers, guiding post-remission strategies, and selecting new drugs for leukemia relapse.
Article
Hematology
Marisa J. L. Aitken, Christopher B. Benton, Ghayas C. Issa, Koji Sasaki, Musa Yilmaz, Nicholas J. Short
Summary: Chronic myeloid leukemia (CML) is defined by the presence of an oncogenic fusion protein caused by a reciprocal translocation between chromosomes 9q and 22q. Familial occurrence of CML is rare, but in the cases described, genetic variants in the patients and their environmental exposures are reported as factors that may have contributed to CML pathogenesis. Further investigation into the familial association of these two cases of CML is warranted to explore definitive etiologies of the disease.
ACTA HAEMATOLOGICA
(2021)
Review
Immunology
Prerna Malaney, Maria Velasco-Estevez, Pedro Aguilar-Garrido, Marisa J. L. Aitken, Lauren E. Chan, Xiaorui Zhang, Sean M. Post, Miguel Gallardo
Summary: B-cell lymphomas are a highly heterogeneous group of malignancies requiring appropriate animal models for research and identifying effective therapies. This article discusses a new driver of B-cell lymphomas, hnRNP K, and introduces a mouse model for studying this disease. The model shows high penetrance of B-cell lymphomas and upregulation of the c-Myc oncogene, making it a valuable pre-clinical platform for assessing novel therapeutics.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Alejandra Ortiz-Ruiz, Yanira Ruiz-Heredia, Maria Luz Morales, Pedro Aguilar-Garrido, Almudena Garcia-Ortiz, Antonio Valeri, Carmen Barcena, Rosa Maria Garcia-Martin, Vanesa Garrido, Laura Moreno, Alicia Gimenez, Miguel Angel Navarro-Aguadero, Maria Velasco-Estevez, Eva Lospitao, Maria Teresa Cedena, Santiago Barrio, Joaquin Martinez-Lopez, Maria Linares, Miguel Gallardo
Summary: The study demonstrates the enhanced mitochondrial activity in multiple myeloma (MM) patients is linked to c-Myc expression. Through the mitochondrial inhibitor tigecycline, Myc functionality can be effectively inhibited to combat MM cell proliferation. Mitochondrial activity progressively increases as the disease progresses, and therapeutic targeting of mitochondria shows promising efficacy in overcoming MM growth.
Review
Oncology
Marisa J. L. Aitken, Farhad Ravandi, Keyur P. Patel, Nicholas J. Short
Summary: Quantification of measurable residual disease (MRD) provides critical prognostic information in acute myeloid leukemia (AML), with different detection platforms having varying sensitivity and applicability. MRD negativity is associated with reduced risk of relapse in AML, but the therapeutic implications remain unclear and require further investigation.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Shelley Herbrich, Natalia Baran, Tianyu Cai, Connie Weng, Marisa J. L. Aitken, Sean M. Post, Jared Henderson, Chunhua Shi, Ondrej Havranek, Guillame Richard-Carpentier, Guy Sauvageau, Keith Baggerly, Gheath Al-Atrash, R. Eric Davis, Naval Daver, Dongxing Zha, Marina Konopleva
Summary: The study identified CD200 as potentially stem cell-specific immune checkpoint overexpressed in AML LSCs, leading to immunosuppression by impairing cell metabolism and function, which could contribute to the progression and relapse of AML. Therapeutic strategies targeting CD200 may offer a promising approach to eliminate LSCs and prevent AML relapse.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Yanira Ruiz-Heredia, Alejandra Ortiz-Ruiz, Mehmet K. Samur, Vanesa Garrido, Laura Rufian, Ricardo Sanchez, Pedro Aguilar-Garrido, Santiago Barrio, Miguel A. Martin, Niccolo Bolli, Yu-Tzu Tai, Raphael Szalat, Mariateresa Fulciniti, Nikhil Munshi, Joaquin Martinez-Lopez, Maria Linares, Miguel Gallardo
Summary: Analyzing mitochondrial DNA copy number (mtDNACN) in monoclonal gammopathies and multiple myeloma revealed differences related to disease progression and demonstrated the involvement of mitochondria in the pathogenesis of these diseases. The findings highlighted the importance of mtDNACN evaluation in guiding clinical decision making, especially in high-risk smoldering MM cases.
Article
Hematology
Sean M. Post, Huaxian Ma, Prerna Malaney, Xiaorui Zhang, Marisa J. L. Aitken, Po Yee Mak, Vivian R. Ruvolo, Tomoko Yasuhiro, Ryohei Kozaki, Lauren E. Chan, Lauren B. Ostermann, Marina Konopleva, Bing Z. Carter, Courtney DiNardo, Michael D. Andreeff, Joseph D. Khoury, Peter P. Ruvolo
Summary: The combination of ONO-7475 and ABT-199 shows strong efficacy in killing FLT3-mutant AML cells and ABT-199-resistant cells. ONO-7475 reduces the expression of pro-growth and anti-apoptotic proteins, improving the resistance to ABT-199. In mouse models, the combination treatment significantly reduces leukemic burden and prolongs survival, indicating its potential for AML therapy.
Article
Biochemistry & Molecular Biology
Sankaranarayan Kannan, Mary E. Irwin, Shelley M. Herbrich, Tiewei Cheng, LaNisha L. Patterson, Marisa J. L. Aitken, Kapil Bhalla, M. James You, Marina Konopleva, Patrick A. Zweidler-McKay, Joya Chandra
Summary: AML patients with FLT3-ITD mutations have elevated levels of HO-1, which contributes to TKI resistance. Inhibiting HO-1 can increase sensitivity to TKI and genetic or pharmacological suppression of NRF2, a key driver of the pathway, results in decreased HO-1 levels and reduced AML resistance.
Review
Biochemistry & Molecular Biology
Pedro Aguilar-Garrido, Alvaro Otero-Sobrino, Miguel Angel Navarro-Aguadero, Maria Velasco-Estevez, Miguel Gallardo
Summary: Hematological malignancies present a challenge due to treatment resistance. RNA-binding proteins have been identified as potential biomarkers and therapeutic targets, and understanding their regulatory mechanisms can help in identifying novel therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Ana Jimenez-Ubieto, Maria Poza, Alejandro Martin-Munoz, Yanira Ruiz-Heredia, Sara Dorado, Gloria Figaredo, Juan Manuel Rosa-Rosa, Antonia Rodriguez, Carmen Barcena, Laura Parrilla Navamuel, Jaime Carrillo, Ricardo Sanchez, Laura Rufian, Alexandra Juarez, Margarita Rodriguez, Chongwu Wang, Paula de Toledo, Carlos Grande, Manuela Mollejo, Luis-Felipe Casado, Maria Calbacho, Tycho Baumann, Inmaculada Rapado, Miguel Gallardo, Pilar Sarandeses, Rosa Ayala, Joaquin Martinez-Lopez, Santiago Barrio
Summary: In this study, we screened follicular lymphoma patients for liquid biopsy MRD biomarkers using NGS panel and found trackable mutations in a majority of the samples. We used ultra-deep sequencing to track these mutations in follow-up samples and found that positive LiqBio-MRD correlated with a higher risk of progression during treatment. The combination of LiqBio-MRD and PET/CT provided a sensitive and specific identification of patients who progressed in less than two years. This non-invasive approach should be considered in future clinical trials.
Article
Oncology
Larissa Haertle, Natalia Buenache, Hipolito Nicolas Cuesta Hernandez, Michal Simicek, Renata Snaurova, Inmaculada Rapado, Nerea Martinez, Nieves Lopez-Munoz, Jose Maria Sanchez-Pina, Umair Munawar, Seungbin Han, Yanira Ruiz-Heredia, Rafael Colmenares, Miguel Gallardo, Margarita Sanchez-Beato, Miguel Angel Piris, Mehmet Kemal Samur, Nikhil C. Munshi, Rosa Ayala, Klaus Martin Kortum, Santiago Barrio, Joaquin Martinez-Lopez
Summary: Compared to other neoplasias, Multiple Myeloma is highly responsive to proteasome inhibitors due to its sensitivity to changes in protein homeostasis. Genetic alterations of PSMC genes affect the susceptibility of Multiple Myeloma to proteasome inhibitors, playing a significant role in disease development and resistance. These alterations can serve as biomarkers to predict and monitor patient response, guiding treatment decisions.
Review
Biochemistry & Molecular Biology
Alvaro Otero-Sobrino, Pablo Blanco-Carlon, Miguel Angel Navarro-Aguadero, Miguel Gallardo, Joaquin Martinez-Lopez, Maria Velasco-Estevez
Summary: Mechanosensitive ion channels play a crucial role in sensing mechanical changes and regulating cellular functions, with significant implications for cancer research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)