Article
Cell Biology
Anastasia M. M. Hughes, Vincent Kuek, Joyce Oommen, Grace-Alyssa Chua, Maria van Loenhout, Sebastien Malinge, Rishi S. S. Kotecha, Laurence C. C. Cheung
Summary: Components of the bone marrow microenvironment (BMM) play a significant role in the development, progression, and treatment response of acute lymphoblastic leukemia (B-ALL). This study investigated the cellular and transcriptome profiles of mesenchymal stem cells (MSCs) isolated from the BMM of an immunocompetent BCR-ABL1(+) model of B-ALL. The findings showed that leukemia-associated MSCs had reduced self-renewal capacity, upregulation of inflammatory signaling pathways, and downregulation of genes involved in extracellular matrix organization and osteoblastogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Marlon Wendell Athaydes Kerr, Fabio Magalhaes-Gama, Hiochelson Najibe Santos Ibiapina, Fabiola Silva Alves Hanna, Lilyane Amorim Xabregas, Eliana Brasil Alves, Joao Paulo Diniz Pimentel, Maria Perpetuo Socorro Sampaio Carvalho, Andrea Monteiro Tarrago, Andrea Teixeira-Carvalho, Olindo Assis Martins-Filho, Allyson Guimaraes da Costa, Adriana Malheiro
Summary: New prognostic markers are needed in B-Cell Acute Lymphoblastic Leukemia (B-ALL) patients to improve treatment accuracy and quality of life. The study identified CCL5, IFN-γ, and IL-2 as potential candidates for good prognosis, and CCL2 as a late biomarker associated with poor prognosis. The controversial data on IL-17A and TNF did not allow for a clear definition as positive or negative biomarkers.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Erica Dander, Chiara Palmi, Giovanna D'Amico, Giovanni Cazzaniga
Summary: Genetic lesions predisposing to pediatric B-ALL can lead to a clinically silent pre-leukemic phase. Inflammation in the microenvironment is crucial for promoting genetic instability and disease manifestation. Interaction between leukemic cells and the surrounding microenvironment influences leukemia development, chemoresistance, and other properties, highlighting the importance of a dual targeting therapeutic strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Chun Shik Park, Hiroki Yoshihara, Qingsong Gao, Chunxu Qu, Ilaria Iacobucci, Pankaj S. Ghate, Jon P. Connelly, Shondra M. Pruett-Miller, Ben Wagner, Camenzind G. Robinson, Ashutosh Mishra, Junmin Peng, Lei Yang, Zoran Rankovic, David Finkelstein, Selina Luger, Mark Litzow, Elisabeth M. Paietta, Nikhil Hebbar, M. Paulina Velasquez, Charles G. Mullighan
Summary: The interactions between acute lymphoblastic leukemia (ALL) and mesenchymal stem cells (MSCs) in the bone marrow microenvironment (BME) drive drug resistance through an epithelial-mesenchymal transition (EMT)-like program in MSC-adherent ALL cells, enhancing their survival. Inhibition of the WNT/b-catenin-mediated EMT-like program may be a promising therapeutic strategy to overcome drug resistance in ALL.
Article
Multidisciplinary Sciences
Stephanie L. Rellick, Gangqing Hu, Debra Piktel, Karen H. Martin, Werner J. Geldenhuys, Rajesh R. Nair, Laura F. Gibson
Summary: In this study, an in vitro cell model was developed to investigate a population of treatment-refractory cells in B-cell acute lymphoblastic leukemia (ALL) characterized by dormant, chemotherapy-resistant tumor cells. Through RNA-Seq analysis, the transcriptional signature of these cells was characterized and found to be similar to expression patterns in MRD cells from patients. Genes and signaling pathways common between these cells were identified as potential therapeutic targets for future studies.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Wen-Liang Yu, Zi-Chun Hua
Summary: In this study, a seven-gene signature based on immune/stromal cell infiltration-related genes (ISCIRGs) was identified to predict the prognosis of patients with acute lymphoblastic leukemia (ALL). These genes were directly related to the composition and status of immune/stromal cells in the bone marrow microenvironment.
Article
Oncology
Debbie Piktel, Javohn C. Moore, Sloan Nesbit, Samuel A. Sprowls, Michael D. Craig, Stephanie L. Rellick, Rajesh R. Nair, Ethan Meadows, John M. Hollander, Werner J. Geldenhuys, Karen H. Martin, Laura F. Gibson
Summary: This study investigates the effects of pitavastatin in chemo-resistant ALL cells and provides evidence for the repurposing of this drug as a potential treatment for eliminating chemoresistant tumor cells. The results demonstrate that pitavastatin inhibits the proliferation of chemo-resistant ALL cells and induces apoptosis, highlighting its potential as a therapeutic agent in the treatment of chemo-resistant ALL.
Review
Oncology
Agata Pastorczak, Krzysztof Domka, Klaudyna Fidyt, Martyna Poprzeczko, Malgorzata Firczuk
Summary: Recent studies have shown that acute lymphoblastic leukemia cells use different mechanisms to evade immune recognition, leading to treatment resistance and poor patient outcomes. Interactions between leukemia cells and immune cells in the bone marrow microenvironment play a key role in leukemia development and relapse. Understanding the genetic heterogeneity and immune evasion mechanisms of ALL cells can provide insights into developing more effective treatment strategies targeting the immunosuppressive microenvironment.
Article
Multidisciplinary Sciences
Annie Luong, Fabio Cerignoli, Yama Abassi, Nora Heisterkamp, Hisham Abdel-Azim
Summary: The study validates a novel application of the xCELLigence system as a continuous co-culture for assessing the long-term effects of drug treatment on BCP-ALL cells. The results demonstrate that impedance can be used as a new approach to monitor drug treatment and sensitivity of primary BCP-ALL cells in the presence of protective microenvironmental cells. Moreover, the system was able to discriminate sensitivity of different ALLs to targeted kinase inhibitors and showed differences in sensitivity of CRLF2-driven BCP-ALL cell lines to ruxolitinib.
Article
Cell Biology
Jussara Rios de los Rios, Jennifer Enciso, Armando Vilchis-Ordonez, Ricardo Vazquez-Ramirez, Dalia Ramirez-Ramirez, Juan Carlos Balandran, Aurora Rodriguez-Martinez, Martha Ruiz-Tachiquin, Ericka Pompa-Mera, Luis Mendoza, Gustavo Pedraza-Alva, Hector Mayani, Muller Fabbri, Rosana Pelayo
Summary: Leukemogenesis is the result of continuous interactions between inducing bone marrow microenvironments and malignant precursor cells. Recent research has discovered an abnormal production of proinflammatory mediators in the bone marrow of acute lymphoblastic leukemia (ALL) patients, although the specific mechanism is still unclear. Three miRNAs, miR-146a-5p, miR-181b-5p, and miR-199b-3p, have been identified as potential candidates for TLR8 ligation, as they are overexpressed in ALL and show agonist functional binding. These miRNAs, purified from ALL exosomes, are capable of inducing cytokine production in both hematopoietic and stromal bone marrow cells. The secretion of these miRNAs by tumor cells as TLR8 agonists may contribute to the formation of proinflammatory microenvironments and the inhibition of normal hematopoietic stem cells.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Review
Oncology
Carolina Simioni, Ilaria Conti, Gabriele Varano, Cinzia Brenna, Eva Costanzi, Luca M. Neri
Summary: The molecular communication between cancer cells and their microenvironment is crucial for the onset of resistance to targeted therapies, highlighting the importance of understanding tumor-microenvironment crosstalk in diseases like Acute Lymphoblastic Leukemia. Studies have identified potential therapeutic targets within the bone marrow microenvironment, such as cytokines, receptors, and proteins related to hypoxia, as well as emphasizing the role of angiogenesis in leukemia pathogenesis. Understanding these mechanisms could lead to early diagnosis and personalized therapies for leukemia.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Zixi Hong, Zimeng Wei, Tian Xie, Lin Fu, Jiaxing Sun, Fuling Zhou, Muhammad Jamal, Qiuping Zhang, Liang Shao
Summary: Acute lymphoblastic leukemia (ALL) is regulated by various signaling molecules such as cytokines and adhesion molecules in its microenvironment. Chemokines play important roles in leukemia microenvironment and affect ALL outcomes. Targeting chemokine axes for ALL treatments shows potential, with some related inhibitors entering clinical trials.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(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.
Review
Oncology
Marilena Ciciarello, Giulia Corradi, Dorian Forte, Michele Cavo, Antonio Curti
Summary: The passage underscores the significance of bone marrow microenvironment in therapy resistance in acute myeloid leukemia (AML), highlighting the impact of stromal and immune cells on the protection of AML cells and their response to treatments. Understanding these interactions can lead to the development of novel drug combinations and more effective therapies for AML.
Review
Oncology
Ling Gu, Ping Liao, Hanmin Liu
Summary: Although the prognosis for acute leukemia has improved, the treatment of relapsed/refractory acute leukemia remains challenging. Targeting the bone marrow microenvironment may provide a promising approach for treating this condition. Cancer-associated fibroblasts (CAFs) have been shown to play a significant role in the tumor microenvironment, but their heterogeneity and plasticity pose challenges for targeted therapies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Applied
Dalila Meneghetti, Verciane Schneider Cezarotto, Natalia Paiva do Nascimento, Natacha Azussa Migita, Juliana Ronchi Correa, Maria Francesca Riccio, Lilian Girotto Zambaldi, Jose Andres Yunes, Leonardo Luis Artico
Summary: The study demonstrated that the hydroalcoholic extract from Vaccinium ashei leaves has toxic effects on T-cell Acute lymphoblastic leukemia, inducing cell apoptosis, micronuclei formation, p53 pathway activation, and cell cycle arrest. Mass spectrometry identified various phenolic compounds in the extract, some of which are presumed to cause DNA damage.
NATURAL PRODUCT RESEARCH
(2022)
Article
Oncology
Luciana Chain Veronez, Paola Fernanda Fedatto, Carolina Alves Pereira Correa, Regia Caroline Peixoto Lira, Mirella Baroni, Keteryne Rodrigues da Silva, Paula Santos, David Santos Marco Antonio, Rosane de Paula Silva Queiroz, Sonir Roberto Rauber Antonini, Silvio Tucci Jr, Luciano Neder, Jose Andres Yunes, Silvia Regina Brandalise, Rodrigo Alexandre Panepucci, Luiz Gonzaga Tone, Carlos Alberto Scrideli
Summary: This study reveals associations between miRNA profiles and childhood ACT prognosis, suggesting that miRNAs could serve as useful biomarkers to distinguish patients with favorable and unfavorable clinical outcomes.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Multidisciplinary Sciences
Arthur Schveitzer Ferreira, Amanda Lopacinski, Michel Batista, Priscila Mazzocchi Hiraiwa, Beatriz Gomes Guimaraes, Nilson Ivo Tonin Zanchin
Summary: Epidermal growth factors (EGF) play important roles in various aspects, including embryogenesis, skin development, and immune response homeostasis. However, recombinant production of these factors in prokaryotic systems is challenging due to their structural organization. This study presents a reliable method for producing seven human growth factors of the EGF family in Escherichia coli, demonstrating their folded and stable conformation and high activity at low concentrations.
SCIENTIFIC REPORTS
(2022)
Article
Infectious Diseases
Natalia Erdens Maron Freitas, Emily Ferreira Santos, Leonardo Maia Leony, Angelo Antonio Oliveira Silva, Ramona Tavares Daltro, Larissa de Carvalho Medrado Vasconcelos, Gabriela Agra Duarte, Cristiane Oliveira da Mota, Edimilson Domingos Silva, Paola Alejandra Fiorani Celedon, Nilson Ivo Tonin Zanchin, Fred Luciano Neves Santos
Summary: The chimeric antigens IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4 were evaluated in the double-antigen sandwich ELISA platform. The diagnostic performance of the DAgS-ELISA was promising, but improvements are being considered to increase its sensitivity.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Medicine, General & Internal
Emily Ferreira dos Santos, angelo Antonio Oliveira Silva, Natalia Erdens Maron Freitas, Leonardo Maia Leony, Ramona Tavares Daltro, Carlos Antonio de Souza Teles Santos, Maria da Conceicao Chagas de Almeida, Fernando Luiz Vieira de Araujo, Paola Alejandra Fiorani Celedon, Marco Aurelio Krieger, Nilson Ivo Tonin Zanchin, Mitermayer Galvao dos Reis, Fred Luciano Neves Santos
Summary: Chagas disease (CD) is a major cause of inability to donate blood. The current blood screening methods for anti-Trypanosoma cruzi antibodies have high false positive rates. A research group has developed four chimeric proteins that have shown high performance and low cross-reactivity rates. These proteins can be used to screen for CD in blood donations, reducing the risk of unnecessary blood disposal or T. cruzi transmission.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Arthur Schveitzer Ferreira, Amanda Lopacinski, Michel Batista, Priscila Mazzocchi Hiraiwa, Natalia Fernanda Bueno, Beatriz Gomes Guimaraes, Nilson I. T. Zanchin
Summary: NRG1 is a growth factor family involved in signaling pathways of various normal cell types and human diseases. In this study, the hNRG1 alpha EGF domain was successfully expressed and purified in E. coli, demonstrating its high activity in cell proliferation and migration.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Giovanna Cesaro, Heloisa Tramontin da Soler, Eloise Pavao Guerra-Slompo, Ahmed Haouz, Pierre Legrand, Nilson Ivo Tonin Zanchin, Beatriz Gomes Guimaraes
Summary: Rrp44/Dis3 is a conserved eukaryotic ribonuclease that plays a role in processing and degradation of almost all types of RNA. Depletion of Rrp44 in Trypanosoma brucei blocks maturation of ribosomal RNA, leading to disruption of ribosome synthesis and inhibition of cell proliferation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Eloise Pavao Guerra-Slompo, Giovanna Cesaro, Beatriz Gomes Guimaraes, Nilson Ivo Tonin Zanchin
Summary: Trypanosoma brucei, a protozoan with fragmented large subunit rRNA, requires additional processing for the maturation of its LSU rRNA. TbRRP44, a nuclease, is essential for this maturation process, where its RNB domain and physical presence of the PIN domain play crucial roles. A new endonucleolytic cleavage site was identified in ITS1, and TbRRP44 is also involved in the degradation of 5'-ETS and part of ITS1 during the maturation of 18S rRNA 3'-end.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Infectious Diseases
Ramona Tavares Daltro, Emily Ferreira Santos, Angelo Antonio Oliveira Silva, Natalia Erdens Maron Freitas, Leonardo Maia Leony, Larissa Carvalho Medrado Vasconcelos, Alejandro Ostermayer Luquetti, Paola Alejandra Fiorani Celedon, Nilson Ivo Tonin Zanchin, Carlos Gustavo Regis-Silva, Fred Luciano Neves Santos
Summary: This study evaluated the diagnostic potential of four chimeric recombinant antigens for diagnosing chronic Chagas disease. The results showed that these antigens can effectively discriminate between T. cruzi-positive and -negative samples.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Oncology
Tim Kong, Angelo B. A. Laranjeira, Kangning Yang, Daniel A. C. Fisher, LaYow Yu, Laure Poittevin De La Fregonniere, Anthony Z. Wang, Marianna B. Ruzinova, Jared S. Fowles, Mary C. Fulbright, Maggie J. Cox, Hamza Celik, Grant A. Challen, Sidong Huang, Stephen T. Oh
Summary: By using single-cell RNA sequencing, researchers found that increased expression of DUSP6 is associated with disease transformation in MPNs and sAML. Targeting DUSP6 inhibits signaling pathways and reduces inflammatory cytokine production. Inhibiting DUSP6 also suppresses RSK1 and improves clinical outcomes.
Article
Biochemical Research Methods
Eloise Pavao Guerra-Slompo, Gisele Fernanda Assine Picchi-Constante, Martin Marek, Christophe Romier, Wolfgang Sippl, Nilson Ivo Tonin Zanchin
Summary: We present a combined in cellulo and in vivo approach to identify compounds with high potential for inhibiting Trypanosoma cruzi. The in cellulo assays consist of two phases - one for excluding inactive or toxic compounds and the other for determining IC50, CC50, and selective index (SI). Compounds with high SI are further tested in in vivo infection models to evaluate their efficacy compared to benznidazole, a reference drug for Chagas disease treatment. For more details, refer to Marek et al. (2021).
Article
Biochemistry & Molecular Biology
Leonardo Luis Artico, Juliana Silveira Ruas, Jose Ricardo Teixeira Junior, Natacha Azussa Migita, Gustavo Seguchi, Xinghua Shi, Silvia Regina Brandalise, Roger Frigerio Castilho, Jose Andres Yunes
Summary: IGFBP7 promotes the permanence of IGF1R on the cell surface, prolonging Akt activation in the PI3K-Akt axis, which contributes to energy metabolism and glycolytic metabolism enhancement in BCP-ALL. Neutralizing IGFBP7 or inhibiting the PI3K-Akt pathway can restore the physiological levels of GLUT1 on the cell surface. This metabolic effect provides a mechanistic explanation for the negative impact of IGFBP7 knockdown or antibody neutralization on B cells in vitro and in vivo, highlighting its potential as a therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Natacha Azussa Migita, Patricia Yoshioka Jotta, Natalia Paiva do Nascimento, Victor Sande Vasconcelos, Gabriel Lopes Centoducatte, Katlin Brauer Massirer, Amilcar Cardoso de Azevedo, Silvia Regina Brandalise, Jose Andres Yunes
Summary: Novel subgroups of ALL were identified using targeted RNA sequencing in 144 B-other and 40 classical ALL samples. Fusion transcript analysis easily identified known fusions and revealed novel fusions. Abnormally high expression of certain genes and detection of gene deletions were also used to classify the subgroups. The findings provide further insight into the genetic alterations in ALL and their association with clinical characteristics.
Article
Biochemical Research Methods
Gisele Fernanda Assine Picchi-Constante, Priscila Mazzocchi Hiraiwa, Martin Marek, Vanessa Zulkievicz Rogerio, Eloise Pavao Guerra-Slompo, Christophe Romier, Nilson Ivo Tonin Zanchin
Summary: This study presents a novel genetic complementation strategy for investigating gene function in Trypanosoma cruzi, the parasite responsible for Chagas disease. By combining CRISPR-Cas9 technology with recombination of resistant variants of the target gene containing desired mutations, detailed exploration of protein function is made possible. This experimental approach overcomes some of the limitations associated with traditional gene knockouts in T. cruzi.