Review
Biochemistry & Molecular Biology
Geoffrey Brown
Summary: The origin cell of chronic myeloid leukemia is a hematopoietic stem cell and the hallmark oncogene is BCR-ABLp210, which influences hematopoietic stem and progenitor cells to myeloid fate. Studies have shown that BCR-ABLp210 affects the epigenome, leading to dysregulation of fate choice for hematopoietic stem cells, but the reason why neutrophils are abundantly produced in the disease remains unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Yammy Yung, Emily Lee, Hiu-Tung Chu, Pui-Kwan Yip, Harinder Gill
Summary: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders characterized by clonal myeloproliferation. Despite effective treatment, complete eradication of CML/MPN stem cells is rare. Novel agents and combination therapy have potential to target abnormal hematopoietic stem cells and the sustaining bone marrow microenvironment in CML and MPNs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Yingxin Sun, Qinrong Wang, Xingxia Zhang, Zhiyu Zhang, Qian Wang, Jiannong Cen, Mingqing Zhu, Jinlan Pan, Dandan Liu, Depei Wu, Yifeng Cai, Suning Chen
Summary: Atypical chronic myeloid leukemia (CML) is a rare BCR-ABL1-negative hematopoietic stem cell disease characterized by heterogeneous molecular landscape and low response to current therapies. Hematopoietic stem cell transplantation (HSCT) did not improve overall survival (OS) in atypical CML patients, and further evaluation is needed. AML-like chemotherapy followed by bridging allogeneic HSCT may be a suitable regimen for appropriate individuals.
ANNALS OF HEMATOLOGY
(2023)
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.
Article
Immunology
Yi Chen, Jiamin Huang, Zaiwen Guo, Zhechen Zhu, Yiming Shao, Linbin Li, Yunxi Yang, Yanzhen Yu, Lu Liu, Bingwei Sun
Summary: In this study, the function and heterogeneity of neutrophils in neonatal umbilical cord blood (UCB) were analyzed using single-cell RNA sequencing analysis for the first time. The results showed that neutrophils in UCB were more naive and had more obvious degranulation and activation functions compared to healthy adults. Significant differences were also observed in the amount and function of a specific subset of neutrophils between UCB and healthy adults. Additionally, a new subset of neutrophils with distinct characteristics was identified. This study provides new insights into the mechanism of neutrophil-mediated diseases in neonates and the potential use of neutrophils in UCB.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Jorge Cortes, Carolina Pavlovsky, Susanne Saussele
Summary: Tyrosine-kinase inhibitors have significantly altered the natural course of chronic myeloid leukaemia, allowing some patients to approach a near-normal life expectancy. Successful treatment requires understanding the patient's treatment goals, monitoring optimal response hallmarks, timely interventions, recognition of adverse events, and management of comorbidities.
Review
Medicine, Research & Experimental
P. Torres-Barrera, H. Mayani, A. Chavez-Gonzalez
Summary: CML is a myeloproliferative disease caused by the transformation of primitive hematopoietic cells induced by the BCR-ABL gene, with effective therapy involving tyrosine kinase inhibitors. While there is significant knowledge about the intrinsic biology of CML cells, further research is needed to understand the alterations in their bone marrow microenvironment.
CURRENT RESEARCH IN TRANSLATIONAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Alhomidi Almotiri, Hamed Alzahrani, Juan Bautista Menendez-Gonzalez, Ali Abdelfattah, Badi Alotaibi, Lubaid Saleh, Adelle Greene, Mia Georgiou, Alex Gibbs, Amani Alsayari, Sarab Taha, Leigh-anne Thomas, Dhruv Shah, Sarah Edkins, Peter Giles, Marc P. Stemmler, Simone Brabletz, Thomas Brabletz, Ashleigh S. Boyd, Florian A. Siebzehnrubl, Neil P. Rodrigues
Summary: The study suggests that loss of Zeb1 in adult stem cells leads to significant defects in stem cell renewal and differentiation, which are associated with leukemia signaling. Therefore, Zeb1 plays a crucial role as a transcriptional regulator in hematopoiesis, coordinating HSC self-renewal and differentiation to suppress the potential development of AML.
JOURNAL OF CLINICAL INVESTIGATION
(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
Oncology
Francois Vergez, Laetitia Largeaud, Sarah Bertoli, Marie-Laure Nicolau, Jean-Baptiste Rieu, Ines Vergnolle, Estelle Saland, Audrey Sarry, Suzanne Tavitian, Francoise Huguet, Muriel Picard, Jean-Philippe Vial, Nicolas Lechevalier, Audrey Bidet, Pierre-Yves Dumas, Arnaud Pigneux, Isabelle Luquet, Veronique Mansat-De Mas, Eric Delabesse, Martin Carroll, Gwenn Danet-Desnoyers, Jean-Emmanuel Sarry, Christian Recher
Summary: Classification of acute myeloid leukemia patients based on immunophenotype identifies six categories of differentiation arrest that significantly correlate with genetic lesions, clinical presentation, stem cell properties, chemosensitivity, treatment response, and outcome.
BLOOD CANCER JOURNAL
(2022)
Article
Biochemical Research Methods
Di Wang, Tao Zhang, Katarina Madunic, Antonius A. de Waard, Constantin Blochl, Oleg A. Mayboroda, Marieke Griffioen, Robbert M. Spaapen, Christian G. Huber, Guinevere S. M. Lageveen-Kammeijer, Manfred Wuhrer
Summary: This study performed a detailed analysis of GSL glycans in 19 AML cell lines and revealed significant differences in GSL glycan profiles among different cell lines. The abundance of GSL glycans was found to be associated with the transcriptomic expression of specific transcription factors and glycosyltransferases, providing insights into the regulation of GSL expression.
JOURNAL OF PROTEOME RESEARCH
(2022)
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)
Review
Biochemistry & Molecular Biology
Binoy Yohannan, Binsah George
Summary: This article provides a comprehensive summary of the current management of Lymphoid Blast Crisis (BC), which is one of the most feared complications of chronic myeloid leukemia (CML). The incidence of BC has significantly decreased in the BCR-ABL tyrosine kinase inhibitor era, but there is still a need for novel therapies to improve the clinical outcomes of patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Olga Mulas, Brunella Mola, Clelia Madeddu, Giovanni Caocci, Antonio Maccio, Giorgio La Nasa
Summary: Numerous prognostic indexes have been developed in hematological diseases, but less attention has been paid to easily accessible blood count parameters. In this review, the prognostic value of count blood cells in myeloid malignancies and hematopoietic stem cell transplantation is analyzed based on literature data and in the context of classical prognostic factors and clinical outcomes.
Article
Cell Biology
Mohammad Houshmand, Nicoletta Vitale, Francesca Orso, Alessandro Cignetti, Ivan Molineris, Valentina Gaidano, Stefano Sainas, Marta Giorgis, Donatella Boschi, Carmen Fava, Alice Passoni, Marta Gai, Massimo Geuna, Federica Sora, Alessandra Iurlo, Elisabetta Abruzzese, Massimo Breccia, Olga Mulas, Giovanni Caocci, Fausto Castagnetti, Daniela Taverna, Salvatore Oliviero, Fabrizio Pane, Marco Lucio Lolli, Paola Circosta, Giuseppe Saglio
Summary: The study shows that the newly developed DHODH inhibitor, Meds433, is highly effective in targeting CML cells by activating the apoptotic pathway and inducing metabolic stress. This finding suggests that DHODH inhibition is a promising approach for targeting CML stem/progenitor cells.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Sylvain Lefort, Amal El-Naggar, Susanna Tan, Shane Colborne, Gian Luca Negri, Davide Pellacani, Martin Hirst, Barry Gusterson, Gregg B. Morin, Poul H. Sorensen, Connie J. Eaves
Summary: The role of YB-1 in newly arising human breast cancers and established cell lines was investigated, showing that YB-1 regulation affects tumor formation and metastasis. Experimental results suggest a close correlation between the expression levels of YB-1, HIF1α, and G3BP1, all of which are involved in the development of breast cancer.
CELL DEATH AND DIFFERENTIATION
(2022)
Letter
Hematology
Pierre Arnautou, Violaine Tran Quang, Johanna Konopacki, Florian Chevillon, Dominique Bories, Ivan Sloma, Jean-Valere Malfuson
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Biology
A. Lorzadeh, C. Hammond, F. Wang, D. J. H. F. Knapp, J. Ch Wong, J. Y. A. Zhu, Q. Cao, A. Heravi-Moussavi, A. Carles, M. Wong, Z. Sharafian, J. Steif, M. Moksa, M. Bilenky, P. M. Lavoie, C. J. Eaves, M. Hirst
Summary: By generating comprehensive reference epigenomes of normal human cord blood, we have identified differences in chromatin modifications between different cell types. Particularly, the repressive H3K27me3 mark is retained in lymphoid cells but lost in monocytes and erythroblasts. Inhibition of polycomb group members also affects the fate decisions of neonatal hematopoietic progenitor cells.
Article
Hematology
Colin A. Hammond, Connie J. Eaves
Summary: Previous studies have shown that there are changes in the properties of hematopoietic stem cells (HSC) and progenitor compartments during aging in mice, but the extension of these findings to humans is uncertain. In this study, the surface phenotypes within the CD34(+) compartment of human blood and bone marrow samples were analyzed across different ages. The results indicate a conserved stability of phenotype frequencies within the CD34(+) compartment, but with differences between cells from blood and bone marrow samples. Coordinated changes in surface markers were observed during transitions within the CD34(+) compartment, suggesting potential new strategies for isolating cell types with more specific functional properties.
EXPERIMENTAL HEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Zhengcheng He, Ryan Ghorayeb, Susanna Tan, Ke Chen, Amanda C. Lorentzian, Jack Bottyan, Syed Mohammed Musheer Aalam, Miguel Angel Pujana, Philipp F. Lange, Nagarajan Kannan, Connie J. Eaves, Christopher A. Maxwell
Summary: Female carriers of BRCA1 mutations have a high risk of breast cancer, which may be due to deficient growth control of mammary progenitor cells. This study found that these carriers have a loss of PLK1-mediated mitotic spindle positioning and an inability of the progeny to acquire features of mature luminal cells. These abnormalities are independent of accumulated DNA damage and specifically dependent on elevated PLK1 activity induced by reduced BRCA1 function.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Xingjian Zhai, Xiaoyan Jiang
Summary: LSCs, notorious for their ability to reconstitute hematological malignancies, play a crucial role in therapeutic resistance and disease relapse. Despite their low abundance, LSCs have unique molecular characteristics that enable self-renewal, quiescence, and drug resistance. This review explores the phenotypic characteristics of LSCs, discusses the leukemic stromal microenvironment, highlights molecular aberrations in the transcriptome, epigenome, proteome, and metabolome of LSCs, and presents promising novel therapeutic strategies that target the molecular vulnerabilities of LSCs.
Article
Oncology
Ryan Yen, Sarah Grasedieck, Andrew Wu, Hanyang Lin, Jiechuang Su, Katharina Rothe, Helen Nakamoto, Donna L. Forrest, Connie J. Eaves, Xiaoyan Jiang
Summary: This study analyzed differentially expressed miRNAs in CML patients, showing that the combination of miR-145 and miR-708 effectively predicts response to NL in treatment-naive patients, while miR-150 and miR-185 are significant classifiers at 1 month and 3 months post-NL therapy.
Article
Hematology
Rabah Redjoul, Florence Beckerich, Gonzalo de Luna, Mathieu Leclerc, Nicolas Hebert, Ivan Sloma, Dehbia Menouche, Pablo Bartolucci, Sebastien Maury
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Colin A. Hammond, Si Wei Wu, Fangwu Wang, Margarita E. MacAldaz, Connie J. Eaves
Summary: Human hematopoietic stem cells (HSCs) undergo functional and molecular changes throughout life, involving a switch from a rapidly cycling state to a quiescent state. The proliferation of these cells is growth factor-dependent, but how aging affects this regulation is not well understood. In this study, HSCs were isolated from individuals of different ages and their response to growth factor stimulation was measured. The results showed that aging is associated with a delayed proliferative response and altered cell cycle progression in HSCs. These findings reveal an age-related alteration in the mechanisms regulating the proliferation of human hematopoietic cells.
Letter
Hematology
Violaine Tran Quang, Benjamin Podvin, Christophe Desterke, Sihem Tarfi, Quentin Barathon, Bouchra Badaoui, Nicolas Freynet, Vincent Parinet, Mathieu Leclerc, Sebastien Maury, Eric Solary, Dorothee Selimoglu-Buet, Nicolas Duployez, Orianne Wagner-Ballon, Ivan Sloma
Review
Pharmacology & Pharmacy
Andrew Wu, Kelly A. A. Turner, Adrian Woolfson, Xiaoyan Jiang
Summary: Despite the development of targeted cancer drugs, drug resistance and treatment failure remain significant problems. The Hedgehog (HH) signaling pathway plays a role in the pathogenesis of human malignancies, but its role in disease progression and drug resistance is still unclear, especially in myeloid malignancies. The HH pathway is essential for regulating stem cell fate in chronic myeloid leukemia (CML), and inhibiting this pathway may be an effective therapeutic strategy. This review explores the origins of HH signaling, its roles in development and disease, and the potential use of HH pathway inhibitors in CML treatment.
Article
Oncology
Andrew Wu, Ryan Yen, Sarah Grasedieck, Hanyang Lin, Helen Nakamoto, Donna L. Forrest, Connie J. Eaves, Xiaoyan Jiang
Summary: This study analyzed differentially expressed miRNAs in CD34+ CML cells and their association with imatinib treatment response. 16 miRNAs were identified as being associated with imatinib nonresponse and a machine learning model was trained to create a panel with high predictive performance. The panel, which combined miRNAs and clinical features, outperformed individual miRNA or clinical panels alone. These findings may assist in identifying predictive biomarkers and optimizing treatment plans for CML patients.
Article
Oncology
Felicit de Charry, Johanna Konopacki, Sarah Bugier, Vincent Foissaud, Ivan Sloma, Jean-Valere Malfuson, Pierre Arnautou
Summary: This case describes a 56-year-old woman who was cured of acute myeloid leukemia (AML) and monoclonal gammopathy of undetermined significance (MGUS) through allogeneic stem cell transplantation and subsequent autologous transplantation. The report highlights the lack of efficacy of graft versus myeloma effect in a patient cured of AML, as well as the ability to successfully mobilize peripheral blood stem cells for autologous transplantation after allogeneic transplantation.
LEUKEMIA RESEARCH REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Syed Mohammed Musheer Aalam, Xiaojia Tang, Jianning Song, Upasana Ray, Stephen J. Russell, S. John Weroha, Jamie Bakkum-Gamez, Viji Shridhar, Mark E. Sherman, Connie J. Eaves, David J. H. F. Knapp, Krishna R. Kalari, Nagarajan Kannan
Summary: A lack of understanding of mechanisms controlling organ-specific patterns of metastasis is a problematic feature of many human cancers. In this study, the researchers developed a methodology that comprehensively characterizes different aspects of the metastatic process at a clonal resolution. They demonstrated the effectiveness of this methodology by discriminating the metastatic behavior of a well-established human metastatic cancer cell line and its derivative using computational analysis and machine learning. The findings highlight the potential of combined genomic and computational methodologies to identify new drivers of site-specific patterns of metastasis.
Review
Cell Biology
Ebrahim Eskandari, Connie J. Eaves
Summary: Caspase-3 plays a crucial role in apoptosis and is involved in the growth and maintenance of both normal and malignant cells. Understanding its evolution and dichotomous roles can provide insights into the biology of malignant and normal cells.
JOURNAL OF CELL BIOLOGY
(2022)