Article
Cell Biology
Chi-Ling Chiang, Eileen Y. Hu, Lingqian Chang, Jadwiga Labanowska, Kevan Zapolnik, Xiaokui Mo, Junfeng Shi, Tzyy-Jye Doong, Arletta Lozanski, Pearlly S. Yan, Ralf Bundschuh, Logan A. Walker, Daniel Gallego-Perez, Wu Lu, Meixiao Long, Sanggu Kim, Nyla A. Heerema, Gerard Lozanski, Jennifer A. Woyach, John C. Byrd, Ly James Lee, Natarajan Muthusamy
Summary: This study used a microchannel electroporation technique to investigate the hematopoietic stem cells in chronic lymphocytic leukemia, confirming the existence of clonal hematopoietic stem cells and their differential drug sensitivity. Furthermore, the existence of CLL LICs was validated in both patient and mouse models. Additionally, differential protein ubiquitination and unfolding response were found in GATA2(high) CLL-HSCs, which significantly affected drug sensitivity.
Article
Multidisciplinary Sciences
Lili Pan, Chao Hong, Lai N. Chan, Gang Xiao, Parmanand Malvi, Mark E. Robinson, Huimin Geng, Srinivasa T. Reddy, Jaewoong Lee, Vishal Khairnar, Kadriye Nehir Cosgun, Liang Xu, Kohei Kume, Teresa Sadras, Shaoyuan Wang, Narendra Wajapeyee, Markus Muschen
Summary: B cell acute lymphoblastic leukemia (B-ALL) patients show aberrant expression of the lactonase PON2, bypassing metabolic gatekeeper functions. Deficiency of PON2 compromises glucose uptake and ATP production in B-ALL cells, while its lactonase activity can be used as synthetic lethality to overcome drug resistance in refractory B-ALL.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
Multidisciplinary Sciences
Zachary A. Hing, Janek S. Walker, Ethan C. Whipp, Lindsey Brinton, Matthew Cannon, Pu Zhang, Steven Sher, Casey B. Cempre, Fiona Brown, Porsha L. Smith, Claudio Agostinelli, Stefano A. Pileri, Jordan N. Skinner, Katie Williams, Hannah Phillips, Jami Shaffer, Larry P. Beaver, Alexander Pan, Kyle Shin, Charles T. Gregory, Gulcin H. Ozer, Selen A. Yilmaz, Bonnie K. Harrington, Amy M. Lehman, Lianbo Yu, Vincenzo Coppola, Pearlly Yan, Peggy Scherle, Min Wang, Philip Pitis, Chaoyi Xu, Kris Vaddi, Selina Chen-Kiang, Jennifer Woyach, James S. Blachly, Lapo Alinari, Yiping Yang, John C. Byrd, Robert A. Baiocchi, Bradley W. Blaser, Rosa Lapalombella
Summary: PRMT5 plays an important role in the progression of CLL to Richter transformation, and the PRMT5 inhibitor PRT382 shows potential therapeutic value.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Fabienne Meier-Abt, Junyan Lu, Ester Cannizzaro, Marcel F. Pohly, Sandra Kummer, Sibylle Pfammatter, Laura Kunz, Ben C. Collins, Ferran Nadeu, Kwang Seok Lee, Peng Xue, Myriam Gwerder, Michael Roiss, Jennifer Huellein, Sebastian Scheinost, Sascha Dietrich, Elias Campo, Wolfgang Huber, Ruedi Aebersold, Thorsten Zenz
Summary: This study uncovered mutations affecting protein expression in CLL and identified signaling pathways associated with trisomy 12. STAT2 protein expression was linked to specific drug responses, providing a protein expression reference map for CLL.
Article
Oncology
Matthew G. Cyr, Maissa Mhibik, Junpeng Qi, Haiyong Peng, Jing Chang, Erika M. Gaglione, David Eik, John Herrick, Thomas Venables, Scott J. Novick, Valentine V. Courouble, Patrick R. Griffin, Adrian Wiestner, Christoph Rader
Summary: This study identified highly potent and specific anti-Siglec-6 antibodies that can effectively target and kill Siglec-6(+) leukemic and healthy B cells, while sparing Siglec-6(-) healthy B cells. The T-biAb RC-1 demonstrated the best therapeutic efficacy, eliminating CLL cells at very low ratios and also showing toxicity against healthy B cells. These findings suggest Siglec-6 as a unique target for CLL treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Hematology
Freda K. Stevenson, Francesco Forconi, Thomas J. Kipps
Summary: Research into chronic lymphocytic leukemia has led to significant improvements in the assessment and treatment of patients, with designer drugs now successfully targeting tumor cells based on their biology. Classifying CLL into unmutated (U) and mutated (M) diseases based on the mutational status of IGHV sequences reveals distinct origins, biology, and clinical behaviors for each. Despite advances, challenges such as cell-escape strategies and immunosuppression remain, necessitating continued research into CLL biology.
Article
Oncology
Michael Asger Andersen, Klaus Rostgaard, Carsten Utoft Niemann, Henrik Hjalgrim
Summary: The study found that CLL patients have increased susceptibility to infections for decades before diagnosis, and a similar pattern was observed in the offspring of CLL patients. The duration of this time window is consistent with immune dysfunction and/or certain infections playing a causal role in CLL pathogenesis, potentially mediating the association between constitutional infection susceptibility and CLL risk.
Article
Oncology
Tiffany M. Tran, Julia Philipp, Jaspal Singh Bassi, Neha Nibber, Jolene M. Draper, Tasha L. Lin, Jayanth Kumar Palanichamy, Amit Kumar Jaiswal, Oscar Silva, May Paing, Jennifer King, Sol Katzman, Jeremy R. Sanford, Dinesh S. Rao
Summary: IGF2BP3 plays a crucial role in MLL-Af4 translocated leukemia, deletion of which significantly improves survival and reduces disease burden in mice. At the cellular and molecular levels, IGF2BP3 regulates leukemia cell survival and proliferation by targeting important genes and influencing both steady-state mRNA levels and pre-mRNA splicing.
Review
Biochemistry & Molecular Biology
Martijn W. C. Verbeek, Stefan J. Erkeland, Vincent H. J. van der Velden
Summary: This article reviews the role of snoRNAs in B-cell development and malignancies, highlighting their potential involvement in oncogenic transformation. Dysregulated snoRNA expression has been associated with abnormal B-cell differentiation and the progression of B-cell malignancies, including lymphoblastic leukemia, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and plasma cell neoplasms. Further understanding of snoRNA function in oncogenesis may lead to the development of novel diagnostic biomarkers or therapeutic targets.
Article
Hematology
Yue Sheng, Jiangbo Wei, Fang Yu, Huanzhou Xu, Chunjie Yu, Qiong Wu, Yin Liu, Lei Li, Xiao-long Cui, Xueying Gu, Bin Shen, Wei Li, Yong Huang, Sumita Bhaduri-McIntosh, Chuan He, Zhijian Qian
Summary: YTHDC1 functions as a nuclear m(6)A reader in RNA metabolism regulation, with its overexpression shown in AML. Genetic deletion of Ythdc1 blocks AML development and maintenance, as well as LSCs self-renewal. YTHDC1 also plays a role in normal hematopoiesis and HSPC maintenance, with haploinsufficiency reducing LSCs self-renewal in vivo.
Article
Oncology
Christian Sordo-Bahamonde, Seila Lorenzo-Herrero, Alejandra Martinez-Perez, Ana P. Gonzalez-Rodriguez, Angel R. Payer, Esther Gonzalez-Garcia, Candelaria Aguilar-Garcia, Sara Gonzalez-Rodriguez, Alejandro Lopez-Soto, Alejandra Garcia-Torre, Segundo Gonzalez
Summary: Patients with CLL show increased expression of inhibitory immune checkpoint BTLA on CD4+ and CD8+ T lymphocytes, leading to suppression of antitumor responses. Blocking BTLA enhances CD8+ T cell-mediated anti-leukemic responses, suggesting its potential as a therapeutic target in CLL.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Joo Eun (June) Kim, Lin Tze Tung, Roselyn R. Jiang, Mitra Yousefi, Yue Liang, Danielle Malo, Silvia M. Vidal, Anastasia Nijnik
Summary: Rheumatoid arthritis severely affects B lymphocyte development in mice, with potential implications for B cell repertoire formation, tolerance induction, and disease mechanisms.
Article
Hematology
Noelle Frey
Summary: Brexucabtagene autoleucel has become the first anti-CD19 chimeric antigen receptor T-cell product approved by the FDA for the treatment of relapsed and refractory B-cell acute lymphoblastic leukemia, significantly expanding treatment options for patients.
Article
Biochemistry & Molecular Biology
Dennis Das Gupta, Christoph Paul, Nadine Samel, Maria Bieringer, Daniel Staudenraus, Federico Marini, Hartmann Raifer, Lisa Menke, Lea Hansal, Baerbel Camara, Edith Roth, Patrick Daum, Michael Wanzel, Marco Mernberger, Andrea Nist, Uta-Maria Bauer, Frederik Helmprobst, Malte Buchholz, Katrin Roth, Lorenz Bastian, Alina M. Hartmann, Claudia Baldus, Koichi Ikuta, Andreas Neubauer, Andreas Burchert, Hans-Martin Jaeck, Matthias Klein, Tobias Bopp, Thorsten Stiewe, Axel Pagenstecher, Michael Lohoff
Summary: This study finds that Irf4(-/-) mice are prone to developing BCP-ALL, and further investigates the impaired differentiation but enhanced proliferation of Irf4(-/-) preB-I cells, possibly due to Jak3 mutations.
CELL DEATH AND DIFFERENTIATION
(2022)