Article
Oncology
Mengping Xi, Shanshan Guo, Caicike Bayin, Lijun Peng, Florent Chuffart, Ekaterina Bourova-Flin, Sophie Rousseaux, Saadi Khochbin, Jian-Qing Mi, Jin Wang
Summary: This study found that the HDAC inhibitor chidamide has an anti-tumor effect on T-ALL cells, particularly by inhibiting the NOTCH1-MYC signaling axis. Clinical trial results support that chidamide treatment reduces minimal residual disease in patients and is well tolerated.
FRONTIERS OF MEDICINE
(2022)
Article
Immunology
Diogo F. T. Veiga, Mathieu Tremblay, Bastien Gerby, Sabine Herblot, Andre Haman, Patrick Gendron, Sebastien Lemieux, Juan Carlos Zuniga-Pflucker, Josee Hebert, Joseph Paul Cohen, Trang Hoang
Summary: Early T-cell development is controlled by E proteins, NOTCH1 and pre-TCR signaling. Perturbations of these pathways are implicated in leukemogenesis. This study investigates the individual roles of HEB, E2A, NOTCH1, and Tcf12 in T-ALL using gene-deficient mice. The findings suggest that HEB and E2A restrain cell proliferation, Tcf12 gene dosage is essential for the clonal expansion of pre-leukemic stem cells, and HEB acts as a tumor suppressor in T-ALL.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Rashedul Islam, Catherine E. Jenkins, Qi Cao, Jasper Wong, Misha Bilenky, Annaick Carles, Michelle Moksa, Andrew P. Weng, Martin Hirst
Summary: Runt-related transcription factor 1 (RUNX1) is oncogenic in various leukemias and epithelial cancers, and its expression is associated with poor prognosis. It cooperates with other oncogenic factors to drive the expression of proto-oncogenes in T cell acute lymphoblastic leukemia (T-ALL), but the specific molecular mechanisms and cooperation with other factors are not well understood.
Article
Medicine, General & Internal
Robert Chiesa, Christos Georgiadis, Farhatullah Syed, Hong Zhan, Annie Etuk, Soragia Athina Gkazi, Roland Preece, Giorgio Ottaviano, Toni Braybrook, Jan Chu, Agnieszka Kubat, Stuart Adams, Rebecca Thomas, Kimberly Gilmour, David O'Connor, Ajay Vora, Waseem Qasim
Summary: Base editing technique has been used to inactivate genes and treat relapsed childhood T-cell leukemia with promising results.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Oncology
Francesco Tamiro, Andrew P. Weng, Vincenzo Giambra
Summary: Leukemia-initiating cells (LIC) are unique cells in different types of leukemia that have self-renewing capabilities and produce tumors, which are functionally distinct from bulk leukemia cells. Current conventional treatments are not effective in eliminating LICs, hence innovative therapeutics targeting LICs hold promise for developing an effective cure for ALL.
Article
Multidisciplinary Sciences
Natalia Baran, Alessia Lodi, Yogesh Dhungana, Shelley Herbrich, Meghan Collins, Shannon Sweeney, Renu Pandey, Anna Skwarska, Shraddha Patel, Mathieu Tremblay, Vinitha Mary Kuruvilla, Antonio Cavazos, Mecit Kaplan, Marc O. Warmoes, Diogo Troggian Veiga, Ken Furudate, Shanti Rojas-Sutterin, Andre Haman, Yves Gareau, Anne Marinier, Helen Ma, Karine Harutyunyan, May Daher, Luciana Melo Garcia, Gheath Al-Atrash, Sujan Piya, Vivian Ruvolo, Wentao Yang, Sriram Saravanan Shanmugavelandy, Ningping Feng, Jason Gay, Di Du, Jun J. Yang, Fieke W. Hoff, Marcin Kaminski, Katarzyna Tomczak, R. Eric Davis, Daniel Herranz, Adolfo Ferrando, Elias J. Jabbour, M. Emilia Di Francesco, David T. Teachey, Terzah M. Horton, Steven Kornblau, Katayoun Rezvani, Guy Sauvageau, Mihai Gagea, Michael Andreeff, Koichi Takahashi, Joseph R. Marszalek, Philip L. Lorenzi, Jiyang Yu, Stefano Tiziani, Trang Hoang, Marina Konopleva
Summary: The study reveals that T-ALL is commonly driven by activating mutations in NOTCH1, which directly relates to elevated OxPhos gene expression. Inhibition of OxPhos disrupts leukemia cell growth and induces metabolic reprogramming into glutaminolysis. Combining OxPhos blockade with inducible knock-down of glutaminase shows synthetic lethality in NOTCH1-mutated T-ALL mice.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Yizhen Li, Xu Yang, Yu Sun, Zhenhua Li, Wenjian Yang, Bensheng Ju, John Easton, Deqing Pei, Cheng Cheng, Shawn Lee, Ching-Hon Pui, Jiyang Yu, Hongbo Chi, Jun J. Yang
Summary: T-cell immunity plays a pivotal role in maintaining long-term remission of acute lymphoblastic leukemia (ALL) and the interplay between host immunity and drug resistance can be harnessed to improve chemotherapy outcomes for ALL.
Article
Oncology
Amber Gibson, Adriana Trabal, David McCall, Sajad Khazal, Laurie Toepfer, Donna H. Bell, Michael Roth, Kris M. Mahadeo, Cesar Nunez, Nicholas J. Short, Courtney DiNardo, Marina Konopleva, Ghayas C. Issa, Farhad Ravandi, Nitin Jain, Gautam Borthakur, Hagop M. Kantarjian, Elias Jabbour, Branko Cuglievan
Summary: This study retrospectively reviewed the safety and efficacy of Venetoclax in pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or lymphoma (LBL). The results showed that Venetoclax is safe and effective to use in pediatric patients with ALL/LBL and should be considered in both the relapsed and upfront settings.
Article
Oncology
Emanuele Murgo, Elisabetta De Santis, Francesca Sansico, Valentina Melocchi, Tommaso Colangelo, Costanzo Padovano, Mattia Colucci, Annalucia Carbone, Beatrice Totti, Alireza Basti, Lisa Gottschlich, Angela Relogio, Nazzareno Capitanio, Fabrizio Bianchi, Gianluigi Mazzoccoli, Vincenzo Giambra
Summary: This study investigates the role of the biological clock in the regulation of cellular dynamics in T-ALL. The disruption of the circadian clock negatively affects LIC activity and JAK/STAT signaling in T-ALL cells. Targeting circadian components could be a potential therapeutic strategy for T-ALL treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Mayumi Sugita, Takahiro Yamazaki, Mohammad Alhomoud, Jeremie Martinet, Jean-Baptiste Latouche, Encouse Golden, Olivier Boyer, Koen Van Besien, Silvia C. Formenti, Lorenzo Galluzzi, Monica L. Guzman
Summary: Autologous T cells engineered with CAR specific for CD19 have been approved for treating CD19(+) hematological malignancies. However, relapse often occurs when neoplastic cells lose CD19 expression. Preclinical models have shown that radiation therapy (RT) can overcome CD19 loss by inducing death receptor expression in cancer cells. Using a human model of CD19(+) acute lymphoblastic leukemia (ALL), it was found that low-dose total body irradiation (LD-TBI) administered before CAR T cell infusion significantly improved overall survival and CAR T cell expansion. These findings support the initiation of clinical trials combining LD-TBI with CAR T cells.
CELL DEATH & DISEASE
(2023)
Review
Oncology
Ziting Zhang, Kun Yang, Han Zhang
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and heterogeneous subtype of cancer. Recent studies have shown the important roles of leukemia-initiating cells (LICs) and leukemic niches in the initiation and progression of T-ALL, leading to the development of targeted therapies.
Article
Chemistry, Medicinal
Chihiro Yoshida, Tomoya Higashi, Yoshifumi Hachiro, Yuki Fujita, Takuya Yagi, Azusa Takechi, Chihiro Nakata, Kazuya Miyashita, Nobuo Kitada, Ryohei Saito, Rika Obata, Takashi Hirano, Takahiko Hara, Shojiro A. Maki
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is a challenging disease to cure, but a synthesized octatetraenylpyrrole analog has shown promising growth-inhibiting activity specifically in T-ALL-derived cells, making it a potential candidate for developing targeted drugs.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Anatomy & Morphology
Yonghua Liu, Bingmu Fang, Xiaoning Feng, Yu Jiang, Yuxiao Zeng, Jinhong Jiang
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignant disease with the involvement of Isocitrate Dehydrogenase 1-R123 (IDH1-R132 H) in its progression. IDH1-R132H mutation promotes T-ALL deterioration by enhancing cell proliferation and invasion, and inhibiting apoptosis. The mutation activates the Notch1 pathway to upregulate HES1 expression, downregulate PTEN expression, and trigger PI3K/AKT pathway, ultimately promoting malignant behaviors in T-ALL cells.
Review
Biochemistry & Molecular Biology
Parveen Shiraz, Waqas Jehangir, Vaibhav Agrawal
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is a rare but aggressive leukemia with CDKN2A/CDKN2B and NOTCH1 being the most common mutated genes. While outcomes for de-novo disease are improving, patients with relapsed and refractory T-ALL have poor prognosis. New targeted therapies show potential to further improve outcomes, and the role of allogeneic stem cell transplant is evolving with the increased use of pediatric-inspired regimens.
Review
Biochemistry & Molecular Biology
Martina Del Gaizo, Ilaria Sergio, Sara Lazzari, Samantha Cialfi, Maria Pelullo, Isabella Screpanti, Maria Pia Felli
Summary: This article reviews the literature on the regulatory role of miRNAs in the immune response of T-ALL, focusing on their roles in Natural Killer, T, T-regulatory, and Myeloid-derived suppressor cells. A better understanding of this molecular crosstalk may provide the basis for the development of potential immunotherapeutic strategies in the field of leukemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Jiro Kikuchi, Mitsuo Hori, Hidekatsu Iha, Noriko Toyama-Sorimachi, Shotaro Hagiwara, Yoshiaki Kuroda, Daisuke Koyama, Tohru Izumi, Hiroshi Yasui, Atsushi Suzuki, Yusuke Furukawa
Letter
Oncology
Taeko Wada, Jiro Kikuchi, Daisuke Koyama, Hiroaki Honda, Yusuke Furukawa
Letter
Hematology
Akiko Nagamachi, Jiro Kikuchi, Akinori Kanai, Yusuke Furukawa, Toshiya Inaba
Article
Medicine, General & Internal
Shogo Yamamoto, Daisuke Koyama, Ryo Igarashi, Takumi Maki, Hiroyuki Mizuno, Yusuke Furukawa, Makoto Kuro-o
Article
Hematology
Yusuke Furukawa, Jiro Kikuchi
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2020)
Letter
Oncology
Atsushi Suzuki, Satoshi Kakugawa, Masafumi Miyoshi, Mitsuo Hori, Kenshi Suzuki, Yusuke Furukawa, Kensuke Ohta
Article
Multidisciplinary Sciences
Junya Tamaoki, Miki Takeuchi, Ryo Abe, Hiroshi Kaneko, Taeko Wada, Shinjiro Hino, Mitsuyoshi Nakao, Yusuke Furukawa, Makoto Kobayashi
SCIENTIFIC REPORTS
(2020)
Article
Oncology
Daisuke Koyama, Jiro Kikuchi, Yoshiaki Kuroda, Masatsugu Ohta, Yusuke Furukawa
Summary: This study reveals the critical role of metabolic homeostasis in the survival of CML cells, particularly in advanced stages of the disease. The BCR-ABL protein activates AMP-activated protein kinase and the mTOR pathway to regulate ATP production and autophagy, with nuclear BCR-ABL detected in advanced-stage CML cells. Activation of AMPK triggers autophagy under energy-deprived conditions, leading to cytoplasmic translocation of BCR-ABL and eventual apoptotic cell death when intracellular ATP is exhausted. This pathway represents a novel therapeutic vulnerability for treating TKI-resistant CML.
Letter
Oncology
Yoshiaki Kuroda, Akiko Yashima-Abo, Daisuke Koyama, Jiro Kikuchi, Shigehisa Mori, Shigeki Ito, Yusuke Furukawa
Article
Cell Biology
Koji Funato, Takaaki Abe, Ryo Kurita, Yoshihisa Watanabe, Yukio Nakamura, Shigeki Miyata, Yusuke Furukawa, Masahiro Satake
Summary: The production of red blood cells in vitro has been improved for basic or clinical research purposes. The study identified proteins showing reproducible differential expression during erythroid differentiation and found that most early-stage proteins were downregulated, while seven proteins showed upregulated expression in both bone marrow and cord blood cells. The roles of these proteins in erythropoiesis require further clarification, as they may contribute to erythroid differentiation.
Letter
Hematology
Naoki Osada, Jiro Kikuchi, Daisuke Koyama, Yoshiaki Kuroda, Hiroshi Yasui, Joel D. Leverson, Yusuke Furukawa
Article
Oncology
Yoshiaki Kuroda, Daisuke Koyama, Jiro Kikuchi, Shigehisa Mori, Tatsuo Ichinohe, Yusuke Furukawa
Summary: MCL cells develop resistance to bortezomib through autophagic degradation of the pro-apoptotic protein NOXA in the tumor microenvironment. Interaction with stromal cells enhances the ubiquitination and subsequent degradation of NOXA, while stromal-derived factors like interleukin-6 promote selective autophagy. Targeting protective autophagy, such as with lysosome inhibitors like chloroquine, may improve the efficacy of bortezomib-containing regimens in MCL.
Article
Multidisciplinary Sciences
Kenji Tago, Satoshi Ohta, Chihiro Aoki-Ohmura, Megumi Funakoshi-Tago, Miho Sashikawa, Takeshi Matsui, Yuki Miyamoto, Taeko Wada, Tomoyuki Oshio, Mayumi Komine, Jitsuhiro Matsugi, Yusuke Furukawa, Mamitaro Ohtsuki, Junji Yamauchi, Ken Yanagisawa
Summary: NKIRAS1 and NKIRAS2 were identified as atypical RAS family members that may act as tumor suppressors in some contexts, but as necessary factors in oncogenic transformation in other situations. The expression levels of NKIRAS likely determine its functional role in carcinogenesis.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Jiro Kikuchi, Nobuyuki Kodama, Masataka Takeshita, Sho Ikeda, Takahiro Kobayashi, Yoshiaki Kuroda, Michihiro Uchiyama, Naoki Osada, Bjarne Bogen, Hiroshi Yasui, Naoto Takahashi, Akiyoshi Miwa, Yusuke Furukawa
Summary: Extramedullary disease (EMD) in multiple myeloma (MM) is associated with resistance to chemotherapy and poor prognosis, and its development mechanisms are not fully understood. This study demonstrates that bone marrow stroma cell-derived hyaluronan (HA) binds to surface CD44 on MM cells, leading to the formation of cell clusters that could develop into EMD. These HA-induced cell clusters exhibit resistance to proteasome inhibitors (PIs) through gamma-secretase-mediated cleavage of CD44, and targeting the HA-CD44 axis effectively suppresses EMD development and overcomes PI resistance.
Article
Oncology
Naoki Osada, Jiro Kikuchi, Hidekatsu Iha, Hiroshi Yasui, Sho Ikeda, Naoto Takahashi, Yusuke Furukawa
Summary: The immunomodulatory drug lenalidomide exerts its pharmacological action in multiple myeloma cells through the degradation of IKZF1 and down-regulation of IRF4. A study found that c-FOS, a member of the AP-1 family, is an integral component of the IKZF1 complex and is responsible for its activator function in MM cells. Inhibiting c-FOS enhances the anti-MM activity of lenalidomide and mitigates drug resistance.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)