Article
Biochemistry & Molecular Biology
Rachid Lahlil, Anne Aries, Maurice Scrofani, Celine Zanetti, Desline Hennequin, Bernard Drenou
Summary: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene. Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) has significantly improved clinical outcomes for CML patients, but IM resistance remains a major challenge. The cause of IM resistance in CML cells is unclear, but additional genetic alterations in leukemic stem cells (LSCs) are a common cause of relapse. A study found that a rare subpopulation of stem cells called very small embryonic-like stem cells (VSELs) in adult CML patients is resistant to IM and less sensitive to apoptosis compared to leukemic hematopoietic stem cells (HSCs). The expression levels of certain miRNAs are also affected in these IM-resistant VSELs, including miR-126 and miR-21, which are involved in LSC leukemia-initiating capacity and growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dan Wang, Huan Yang, Yun Zhang, Rong Hu, Dongjie Hu, Qunxian Wang, Yannan Liu, Mingjing Liu, Zijun Meng, Weihui Zhou, Weihong Song
Summary: Increased levels of CBS and H2S have been found in pediatric CML patients and cells, inhibition of CBS can reduce cell proliferation, induce apoptosis, and inhibit cell migration.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Multidisciplinary Sciences
Ibuki Harada, Haruka Sasaki, Koichi Murakami, Akira Nishiyama, Jun Nakabayashi, Motohide Ichino, Takuya Miyazaki, Ken Kumagai, Kenji Matsumoto, Maki Hagihara, Wataru Kawase, Takayoshi Tachibana, Masatsugu Tanaka, Tomoyuki Saito, Heiwa Kanamori, Hiroyuki Fujita, Shin Fujisawa, Hideaki Nakajima, Tomohiko Tamura
Summary: Chronic myeloid leukemia is driven by the oncogenic tyrosine kinase BCR-ABL, leading to compromised anti-tumor immunity due to restricted differentiation of conventional dendritic cells, increased expression of immunosuppressive PD-L1 in monocytes and basophils, and gene expression related to poor prognosis in basophils.
SCIENTIFIC REPORTS
(2021)
Review
Cell & Tissue Engineering
Hanieh Mojtahedi, Niloufar Yazdanpanah, Nima Rezaei
Summary: CML is driven by the BCR-ABL1 oncoprotein, and TKI therapy has been successful. However, mechanisms leading to resistance and disease progression in CML LSCs call for targeted therapies to eradicate them.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Immunology
Yoon-A Kang, Hyojung Paik, Si Yi Zhang, Jonathan J. Chen, Oakley C. Olson, Carl A. Mitchell, Amelie Collins, James W. Swann, Matthew R. Warr, Rong Fan, Emmanuelle Passegue
Summary: The study reveals the existence of a secretory subset of myeloid-biased multipotent progenitors, MPP3, that plays a crucial role in myeloid lineage differentiation and cytokine production. These cells serve as a reservoir for rapid production of granulocyte/macrophage progenitors and contribute to the amplification of myeloid cell production in stress and disease conditions.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Carl Ernst, Malvin Jefri
Summary: Neurodevelopmental disorders may be caused in part by deficits in epigenetic priming, which prepares the genome for cellular signaling cues and may lead to impairment of terminally differentiated cells. High-resolution epigenetic and transcriptomic mapping studies provide evidence supporting this theory.
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Oncology
Kazuharu Kamachi, Hiroshi Ureshino, Tatsuro Watanabe, Nao Yoshida, Yuta Yamamoto, Yuki Kurahashi, Yuki Fukuda-Kurahashi, Yoshihiro Hayashi, Hideyo Hirai, Satoshi Yamashita, Toshikazu Ushijima, Seiji Okada, Shinya Kimura
Summary: Targeting DNMT1 with OR21 demonstrates anti-tumor effects and impairs leukemic stem cells in chronic myeloid leukemia (CML). Combination therapy of OR21 and TKIs represents a promising treatment strategy for CML.
Review
Immunology
Johanna Rausch, Evelyn Ullrich, Michael W. M. Kuehn
Summary: AML is a malignant disease that is difficult to treat, especially in patients who cannot undergo intensive chemotherapy. Immunotherapy has been successful in treating solid tumors and lymphatic neoplasms, but its efficacy in AML has been limited. Epigenetic dysregulation is a driver of leukemogenesis, and combining targeted epigenetic drugs with immunotherapy may improve treatment outcomes. Further research is needed to understand the immune functions affected by these drugs and their potential for clinical use.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Juan Zhang, Xuefeng Gao, Mingming Wei, Yonghui Li, Guang Yang, Cheng Yang, Li Yu
Summary: A novel epigenetic agent named Apigenin-Vorinostat-Conjugate (AVC) showed potential therapeutic effects against acute myeloid leukemia by effectively inhibiting leukemia cell growth and inducing apoptosis, while sparing normal cells. It exhibits a promising next-generation epigenetic drug for clinical therapy against AML.
Article
Oncology
Toshimi Hoshiko, Yasushi Kubota, Risako Onodera, Taishi Higashi, Masako Yokoo, Keiichi Motoyama, Shinya Kimura
Summary: 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) is commonly used in pharmaceutical formulations and has shown anti-leukemia activity, but lacks tumor cell-selectivity. Folate-appended HP-beta-CyD (FA-HP-beta-CyD) has been synthesized to target cancer cells more effectively, showing stronger inhibitory effects on leukemia cells. FA-HP-beta-CyD may be a promising agent for targeted therapy against leukemia.
Article
Medicine, General & Internal
Stefania Stella, Silvia Rita Vitale, Fabio Stagno, Michele Massimino, Adriana Puma, Cristina Tomarchio, Maria Stella Pennisi, Elena Tirro, Chiara Romano, Francesco Di Raimondo, Emma Cacciola, Rossella Cacciola, Livia Manzella
Summary: In this study, the performance of manual and flow cytometry (FC)-based automatic cell counting methods were compared in chronic myeloid leukemia (CML) patients. The results showed that the FC-based automatic method had comparable performance to manual measurements, without the need for expensive beads or time-consuming intercalator 7AAD.
Article
Medicine, Research & Experimental
Jianming Wang, Yang Liang, Yuefeng Qin, Guoyun Jiang, Yuhang Peng, Wenli Feng
Summary: This study uncovers that circCRKL is specifically expressed and regulates the expression level of BCR-ABL via decoying miR-877-5p in BCR-ABL(+) cells. The findings suggest that targeting circCRKL along with imatinib treatment could be a potential therapeutic strategy for CML patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jialu Ma, Nathan Pettit, John Talburt, Shanzhi Wang, Sherman M. Weissman, Mary Qu Yang
Summary: This study used single-cell RNA sequencing and network analysis to decipher the mechanisms of different TKI responses in CML stem cells. Differentially expressed genes were identified in various types of stem cells of CML patients, and most of these genes were directly controlled by one or more transcription factors. Molecular markers and interacted proteins related to treatment response were also uncovered. These findings can be used for treatment response prediction and drug resistance monitoring.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Hera Wong, Ryohichi Sugimura
Summary: Haematological malignancies are a diverse group of cancers that can occur at any stage of hematopoiesis. Chronic inflammation induced by inflammatory cytokines activates signaling pathways in malignant cells, leading to cancer stem cell phenotypes and disease progression. Studying the molecular mechanisms of immune cell interaction with malignant cells could provide new avenues for targeted therapies for haematological malignancies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Jia Yin, Chao-Ling Wan, Ling Zhang, Hao Zhang, Lian Bai, Hai-Xia Zhou, Ming-Zhu Xu, Li-Yun Chen, Chong-Sheng Qian, Hui-Ying Qiu, Su-Ning Chen, Xiao-Wen Tang, De-Pei Wu, Yan-Ming Zhang, Ai-Ning Sun, Sheng-Li Xue
Summary: The study investigated the role of chidamide, decitabine plus priming regimen in the salvage treatment of relapsed/refractory acute myeloid leukemia. The CDIAG regimen showed good antileukemia activity in these patients with acceptable adverse events.
FRONTIERS IN ONCOLOGY
(2021)
Article
Gastroenterology & Hepatology
Marcos F. Fondevila, Uxia Fernandez, Maria J. Gonzalez-Rellan, Natalia Da Silva Lima, Xabier Buque, Agueda Gonzalez-Rodriguez, Cristina Alonso, Marta Iruarrizaga-Lejarreta, Teresa C. Delgado, Marta Varela-Rey, Ana Senra, Vera Garcia-Outeiral, Eva Novoa, Cristina Iglesias, Begona Porteiro, Daniel Beiroa, Cintia Folgueira, Marta Tojo, Jorge L. Torres, Lourdes Hernandez-Cosido, Oscar Blanco, Juan Pablo Arab, Francisco Barrera, Diana Guallar, Miguel Fidalgo, Miguel Lopez, Carlos Dieguez, Miguel Marcos, Maria L. Martinez-Chantar, Marco Arrese, Carmelo Garcia-Monzon, Jose M. Mato, Patricia Aspichueta, Ruben Nogueiras
Summary: The LPI/GPR55 system activates ACC to affect lipid metabolism, playing a role in the development of NAFLD and NASH. Inhibition of GPR55 and ACCα can block the effects of LPI, which may be a potential new strategy for treating NAFLD and NASH.
Article
Hematology
Man Chun John Ma, Saber Tadros, Alyssa Bouska, Tayla Heavican, Haopeng Yang, Qing Deng, Dalia Moore, Ariz Akhter, Keenan Hartert, Neeraj Jain, Jordan Showell, Sreejoyee Ghosh, Lesley Street, Marta Davidson, Christopher Carey, Joshua Tobin, Deepak Perumal, Julie M. Vose, Matthew A. Lunning, Aliyah R. Sohani, Benjamin J. Chen, Shannon Buckley, Loretta J. Nastoupil, R. Eric Davis, Jason R. Westin, Nathan H. Fowler, Samir Parekh, Maher Gandhi, Sattva Neelapu, Douglas Stewart, Kapil Bhalla, Javeed Iqbal, Timothy Greiner, Scott J. Rodig, Adnan Mansoor, Michael R. Green
Summary: This study comprehensively analyzed the genomic landscapes of multiple B-cell non-Hodgkin lymphoma (B-NHL) subtypes, and identified common features and subtype-specific patterns of genetic alterations. The study also revealed potential patterns of genetic cooperation that contribute to lymphomagenesis, providing important insights into the pathogenesis of B-NHL.
Article
Oncology
Sonia Gonzalez de Villambrosia, Mariana Bastos, Javier Menarguez Palanca, Jorge Gayoso Cruz, Jose-Tomas Navarro, Gustavo Tapia, Sara Alvarez Alonso, Alejandro Martin, Oscar Blanco, Pau Abrisqueta, Josep Castellvi, Ana Garcia-Noblejas, Reyes Arranz, Magdalena Adrados, Andres Lopez, Santiago Montes-Moreno
Summary: High Grade B Cell Lymphoma, NOS and High Grade B Cell Lymphoma with Dual Hit or Triple Hit were recently reclassified in the 2016 WHO classification. This study found that HGBCL NOS had better response to first line treatment compared to HGBCL with DH/TH, and only the presence of BCL2 translocation significantly affected PFS. Other clinical features were similar between the two categories, and both high grade and DLBCL morphological patterns showed equivalent PFS and OS.
LEUKEMIA & LYMPHOMA
(2022)
Article
Oncology
Ana Casado-Garcia, Marta Isidro-Hernandez, Ninad Oak, Andrea Mayado, Christine Mann-Ran, Javier Raboso-Gallego, Silvia Aleman-Arteaga, Alexandra Buhles, Dario Sterker, Elena G. Sanchez, Jorge Martinez-Cano, Oscar Blanco, Alberto Orfao, Diego Alonso-Lopez, Javier De Las Rivas, Susana Riesco, Pablo Prieto-Matos, Africa Gonzalez-Murillo, Francisco Javier Garcia Criado, Maria Begona Garcia Cenador, Thomas Radimerski, Manuel Ramirez-Orellana, Cesar Cobaleda, Jun J. Yang, Carolina Vicente-Duenas, Andreas Weiss, Kim E. Nichols, Isidro Sanchez-Garcia
Summary: This study demonstrates that early-life administration of the JAK1/2 inhibitor ruxolitinib significantly reduces the risk of B-ALL in mice. This finding presents a potential strategy for preventing the development of B-ALL.
Article
Hematology
Hua-Jay J. Cherng, Ryan Sun, Bryant Sugg, Russell Irwin, Haopeng Yang, Cao Cuong Le, Qing Deng, Luis Fayad, Nathan H. Fowler, Simrit Parmar, Raphael Steiner, Fredrick Hagemeister, Ranjit Nair, Hun Ju Lee, Maria Rodriguez, Felipe Samaniego, Swaminathan P. Iyer, Christopher R. Flowers, Linghua Wang, Loretta J. Nastoupil, Sattva S. Neelapu, Sairah Ahmed, Paolo Strati, Michael R. Green, Jason Westin
Summary: IpWGS of cfDNA can be used for risk stratification to identify high-risk patients and guide patient selection and evaluation of targeted therapies in future clinical trials.
Article
Chemistry, Multidisciplinary
Olga Ramos-Barriga, Barbara-Yolanda Padilla-Fernandez, Sebastian Valverde-Martinez, Miguel Peran-Teruel, Magaly-Teresa Marquez-Sanchez, Maria-Carmen Flores-Fraile, Javier Flores-Fraile, Mario Martin-Hernandez, Edwin Grinard-de-Leon, Maria-Begona Garcia-Cenador, Maria-Fernanda Lorenzo-Gomez
Summary: Clinical trials on hormone therapy for prostate cancer show varying levels of uncertainty. Only about half of the trials demonstrate superiority in the proposed treatment strategies, and a substantial portion of related scientific publications do not report conclusive results.
APPLIED SCIENCES-BASEL
(2022)
Review
Biochemistry & Molecular Biology
Marta Isidro-Hernandez, Silvia Aleman-Arteaga, Ana Casado-Garcia, Belen Ruiz-Corzo, Susana Riesco, Pablo Prieto-Matos, Jorge Martinez-Cano, Lucia Sanchez, Cesar Cobaleda, Isidro Sanchez-Garcia, Carolina Vicente-Duenas
Summary: Leukemia is the most common cancer in children, with B-cell acute lymphoblastic leukemia (B-ALL) being the most prevalent form. The development of pediatric leukemia is believed to occur through a multi-step or multi-hit mechanism, including prenatal and postnatal steps. Although many initiating events for childhood leukemia occur in utero at a higher frequency than the actual incidence of the disease, the reason why only a small percentage of children with these preleukemic hits develop full-blown leukemia remains unknown. Mouse models that replicate the multi-step process of childhood B-ALL will be crucial in identifying environmental or other factors associated with an increased risk of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Jason Westin, R. Eric Davis, Lei Feng, Fredrick Hagemeister, Raphael Steiner, Hun Ju Lee, Luis Fayad, Loretta Nastoupil, Sairah Ahmed, Alma Rodriguez, Michelle Fanale, Felipe Samaniego, Swaminathan P. Iyer, Ranjit Nair, Yasuhiro Oki, Nathan Fowler, Michael Wang, Man Chun John Ma, Francisco Vega, Timothy McDonnell, Chelsea Pinnix, Donna Griffith, Yang Lu, Sanjit Tewari, Ryan Sun, David W. Scott, Christopher R. Flowers, Sattva Neelapu, Michael R. Green
Summary: This study introduces a new treatment strategy (RLI) for newly diagnosed DLBCL patients, which combines targeted therapy with drugs before chemotherapy. The results showed high treatment response rates and durable responses in DLBCL patients treated with RLI. This establishes the potential for developing biologically driven and noncytotoxic first-line therapies for DLBCL.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Joshua W. D. Tobin, Michael R. Green, Maher K. Gandhi
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Jesica Perez-Garcia, Abel Martel-Martel, Paula Garcia-Valles, Luis A. Corchete, Juan L. Garcia, Nerea Gestoso-Uzal, Rosario Vidal-Tocino, Oscar Blanco, Lucia Mendez, Manuel Sanchez-Martin, Manuel Fuentes, Ana B. Herrero, Andreana N. Holowatyj, Jose Perea, Rogelio Gonzalez-Sarmiento
Summary: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally, and the molecular mechanisms behind it remain unclear. This study reveals that the NOMO1 gene can be inactivated through deletion or mutation in EOCRC tumors. While the loss of NOMO1 may be a passenger mutation in the development of EOCRC, it significantly enhances colon cancer cell migration.
Review
Oncology
Jingwen Yang, Yamei Chen, Ying Jing, Michael R. Green, Leng Han
Summary: This article provides an overview of the multidimensional profiling technologies used in CAR T cell therapy research and discusses the utilization of multi-omics data to elucidate CAR targets, factors associated with response or resistance to therapy, and underlying toxicities. These findings can potentially enhance the efficacy and safety of CAR T cell therapies.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Letter
Hematology
Eva Gonzalez Barca, Laura Tomas-Roca, Anna Esteve, Marta Rodriguez, Lucia Gato, Ruth Alonso-Alonso, Alejandro Martin Garcia-Sancho, Raul Cordoba, Anna Monter-Rovira, Mariana Bastos-Oreiro, Juan Miguel Bergua Burgues, Maria Jose Sayas, Maria Cruz Viguria Alegria, Jose Javier Sanchez-Blanco, Monica Roig Pellicer, Hugo Daniel Luzardo Henriquez, Raquel de Ona, Maria Elena Cabezudo, Maria Stefania Infante, Jose Antonio Queizan Hernandez, Rebeca Sanz-Pamplona, Oscar Blanco, Ana Mozos, Fina Climent, Miguel Angel Piris
Summary: This study used the NanoString platform to analyze the correlation matrix of unsupervised co-regulated genes, which included 208 genes. Several clusters of co-regulated genes were found to be associated with inflammatory cells, Epstein-Barr virus, B-cells, cytotoxic T-cells, T-cells, and proliferation. Additionally, the genomic alterations in 62 analyzed genes were investigated using targeted sequencing and different types of mutations were identified.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Javier Melchor, Marcos Garcia-Lacarte, Sara C. Grijalba, Adrian Arnaiz-Leche, Marien Pascual, Carlos Panizo, Oscar Blanco, Victor Segura, Francisco J. Novo, Juan Garcia Valero, Patricia Perez-Galan, Jose A. Martinez-Climent, Sergio Roa
Summary: This study demonstrates that venetoclax can selectively kill MYC+/BCL2(+) lymphoma cells and enhance the infiltration of antigen-activated effector CD8 T cells in the tumor microenvironment, improving the therapeutic response. The combination of anti-CD20-based immunotherapy and BCL2 inhibition shows cooperative immunomodulatory effects and offers promising therapeutic opportunities for DEL-DLBCL patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Guangchun Han, Qing Deng, Mario L. Marques-Piubelli, Enyu Dai, Minghao Dang, Man Chun John Ma, Xubin Li, Haopeng Yang, Jared Henderson, Olga Kudryashova, Mark Meerson, Sergey Isaev, Nikita Kotlov, Krystle J. Nomie, Alexander Bagaev, Edwin R. Parra, Luisa M. Solis Soto, Simrit Parmar, Fredrick B. Hagemeister, Sairah Ahmed, Swaminathan P. Iyer, Felipe Samaniego, Raphael Steiner, Luis Fayad, Hun Lee, Nathan H. Flower, Christopher R. Flowers, Paolo Strati, Jason R. Westin, Sattva S. Neelapu, Loretta J. Nastoupil, Francisco Vega, Linghua Wang, Michael R. Green
Summary: In this study, the tumor and immune cell populations of follicular lymphoma (FL) were characterized using single-cell RNA sequencing. Different subsets of T cells were identified, including cytotoxic CD4 T cells. Somatic mutations were found to be associated with reduced MHC expression on FL cells. The expression of MHCII genes by FL cells was correlated with significant differences in the proportions and immunophenotypic characteristics of T cells.
BLOOD CANCER DISCOVERY
(2022)
