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
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
Hematology
Clinton C. Mason, Carme R. Fiol, Monika J. Baker, Elisabet Nadal-Melsio, Eva Yebra-Fernandez, Luciana Bicalho, Avirup Chowdhury, Michael Albert, Alistair G. Reid, Simone Claudiani, Jane F. Apperley, Jamshid S. Khorashad
Summary: The study identified genes in the NOX family as potential candidates for therapeutic development in AML, with NOX1 showing consistent knockdown effectiveness impacting leukemia cell survival, and further investigation highlighting NOX2 as another member with clear knockdown efficacy.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Erica Dander, Alessandra Fallati, Tamara Gulic, Fabio Pagni, Stefania Gaspari, Daniela Silvestri, Giulia Cricri, Gloria Bedini, Federica Portale, Chiara Buracchi, Rita Starace, Fabio Pasqualini, Mariella D'Angio, Lisa Brizzolara, Oscar Maglia, Alberto Mantovani, Cecilia Garlanda, Maria Grazia Valsecchi, Franco Locatelli, Andrea Biondi, Barbara Bottazzi, Paola Allavena, Giovanna D'Amico
Summary: In B-cell acute lymphoblastic leukaemia (B-ALL), monocyte/macrophage compartments play a crucial role in the remodelling of the bone marrow microenvironment, contributing to the development and progression of the disease. Understanding the involvement of immune cells in the leukaemic microenvironment provides valuable insights for potential targeted therapies in combination with traditional chemotherapy.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Editorial Material
Hematology
Alicia G. Aguilar G. Navarro, Anastasia N. Tikhonova
Summary: The authors of this paper describe distinct transcriptomic changes associated with treatment response in core bone marrow biopsies from patients with acute myeloid leukemia. This finding suggests that stratifying patients for treatment based on their transcriptomic profiles could potentially improve patients' response to treatment and prognosis.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
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)
Review
Biochemistry & Molecular Biology
Kathryn A. Skelding, Daniel L. Barry, Danielle Z. Theron, Lisa F. Lincz
Summary: Acute myeloid leukaemia (AML) has a low survival rate and its resistance to traditional therapies has led to the exploration of the bone marrow microenvironment as a potential source of therapeutic targets. This review discusses the role of the microenvironment in AML development and progression, and focuses on drugs that modulate or target this niche in in vivo models or clinical studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Oncology
Nicholas R. Anderson, Vipul Sheth, Hui Li, Mason W. Harris, Shaowei Qiu, David K. Crossman, Harish Kumar, Puneet Agarwal, Takashi Nagasawa, Andrew J. Paterson, Robert S. Welner, Ravi Bhatia
Summary: Using a mouse model of FLT3-ITD AML, researchers found that FLT3-ITD AML LSC were enriched within the ST-HSC population and had increased expression of CXCR4. Deletion of CXCL12 from the microenvironment enhanced targeting of AML cells by Flt3-TKI plus chemotherapy treatment, including enhanced LSC targeting. Inhibition of p38 signaling reduced the maintenance of Flt3-ITD AML LSC and enhanced their sensitivity to treatment.
Review
Biochemistry & Molecular Biology
Vincent Kuek, Anastasia M. Hughes, Rishi S. Kotecha, Laurence C. Cheung
Summary: Uniform prospective clinical trials have improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia in recent decades. However, high-risk patients continue to have inferior outcomes due to mechanisms where leukaemic cells hijack the bone marrow microenvironment. Targeting the cellular interactions within the leukaemia-bone marrow niche is an exciting novel strategy with significant potential to enhance treatment efficacy and improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
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)
Article
Immunology
Betsabel Chicana, Nastaran Abbasizadeh, Christian Burns, Hanna Taglinao, Joel A. Spencer, Jennifer O. Manilay
Summary: This study investigates the mechanisms of B cell defects in bone marrow caused by the loss of von-Hippel Lindau protein (VHL). The result shows that there is an increase in the frequency and number of B cell progenitors in VhlcKO bone marrow, while Fransctions B-F are decreased. VhlcKO B cells exhibit increased apoptosis and quiescence. Reciprocal BM chimeras confirm that the B cell defects in VhlcKO are derived from extrinsic sources.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Leandro M. Martinez, Monica L. Guzman
Summary: Although chemotherapeutic regimens can eliminate blasts in leukemia patients, such therapies often fail to eliminate all malignant cells, leading to disease relapse. Understanding the interaction between leukemia stem cells (LSCs) and their microenvironment is critical for developing effective therapies. In this review, we will focus on the reciprocal interactions between LSCs and their milieu in the bone marrow.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Oncology
Shivani Malik, Jill M. Westcott, Rolf A. Brekken, Francis J. Burrows
Summary: Pancreatic cancer is a challenging disease with limited therapeutic options and poor long-term survival. This review focuses on the role of a chemokine called CXCL12, secreted by cancer-associated fibroblasts, in promoting various hallmarks of pancreatic cancer such as tumor growth and evasion of immune response. Different approaches to target CXCL12 signaling are discussed, and a novel approach using a farnesyl transferase inhibitor called tipifarnib to inhibit CXCL12 production in pancreatic fibroblasts is proposed.