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.
Review
Cell Biology
Jing Wang, Pei Huang, Changhui Lang, Yan Luo, Zhixu He, Yan Chen
Summary: Trace elements are important substances with low content in the human body and changes in their levels are related to diseases. This paper focuses on their relationship with acute lymphoblastic leukemia (ALL), a malignant blood tumor. Both the trace element levels in ALL patients and the efficacy of different treatment methods are linked to the corresponding trace element changes. It is believed that the abnormal metabolism of trace elements in the body is related to ALL, and this paper aims to provide more information on trace elements for the diagnosis, treatment, and prevention of ALL.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Oncology
Maryam Katoueezadeh, Niloofar Pilehvari, Ahmad Fatemi, Gholamhossein Hassanshahi, Seyedeh Atekeh Torabizadeh
Summary: In response to the alarming increase in acute lymphoblastic leukemia cases, researchers are investigating new therapeutic strategies targeting DNA damage response pathways to overcome resistance to chemotherapy and radiotherapy. This review aims to evaluate the synergistic effects of DNA damage response pathway inhibitors with radiation in the treatment of leukemia.
Article
Biochemistry & Molecular Biology
Lucas B. Pontel, Alberto Bueno-Costa, Agustin E. Morellato, Juliana Carvalho Santos, Gael Roue, Manel Esteller
Summary: Blood-derived cancer cells are selectively sensitive to compounds blocking the GSH-dependent anti-ferroptosis axis, which may have therapeutic significance for ALL.
Article
Biochemistry & Molecular Biology
Fieke W. Hoff, Ti'ara L. Griffen, Brandon D. Brown, Terzah M. Horton, Jan Burger, William Wierda, Stefan E. Hubner, Yihua Qiu, Steven M. Kornblau
Summary: DNA damage response (DNADR) recognition and repair (DDR) pathways play a role in carcinogenesis and therapy responsiveness in leukemia. In this study, we analyzed the protein expression levels of 16 DNADR and DDR proteins in acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia (T-ALL), and chronic lymphocytic leukemia (CLL) cases. Findings showed distinct protein expression clusters across the leukemias, with individual protein expression differing by disease and age. The clusters also had implications for survival and remission duration in both pediatric and adult populations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Martin Kello, Tomas Kuruc, Klaudia Petrova, Michal Goga, Zuzana Michalova, Matus Coma, Dajana Rucova, Jan Mojzis
Summary: The study investigated the anti-leukemic potential of lichen extract and physodic acid in ALL treatment, demonstrating their ability to induce cell death while causing minimal toxicity in normal cells.
Article
Genetics & Heredity
Zeljko Antic, Stefan H. Lelieveld, Cedric G. van der Ham, Edwin Sonneveld, Peter M. Hoogerbrugge, Roland P. Kuiper
Summary: Investigating mutations in clusters separated in time may help understand mutational mechanisms and discover underlying causes.
Article
Multidisciplinary Sciences
Tomoya Isobe, Masatoshi Takagi, Aiko Sato-Otsubo, Akira Nishimura, Genta Nagae, Chika Yamagishi, Moe Tamura, Yosuke Tanaka, Shuhei Asada, Reina Takeda, Akiho Tsuchiya, Xiaonan Wang, Kenichi Yoshida, Yasuhito Nannya, Hiroo Ueno, Ryo Akazawa, Itaru Kato, Takashi Mikami, Kentaro Watanabe, Masahiro Sekiguchi, Masafumi Seki, Shunsuke Kimura, Mitsuteru Hiwatari, Motohiro Kato, Shiro Fukuda, Kenji Tatsuno, Shuichi Tsutsumi, Akinori Kanai, Toshiya Inaba, Yusuke Shiozawa, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Rishi S. Kotecha, Mark N. Cruickshank, Fumihiko Ishikawa, Tomohiro Morio, Mariko Eguchi, Takao Deguchi, Nobutaka Kiyokawa, Yuki Arakawa, Katsuyoshi Koh, Yuki Aoki, Takashi Ishihara, Daisuke Tomizawa, Takako Miyamura, Eiichi Ishii, Shuki Mizutani, Nicola K. Wilson, Berthold Gottgens, Satoru Miyano, Toshio Kitamura, Susumu Goyama, Akihiko Yokoyama, Hiroyuki Aburatani, Seishi Ogawa, Junko Takita
Summary: This study uncovers the molecular heterogeneity of KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) through multi-omics analysis, establishes five distinct subgroups, and reveals the predictive value of RAS pathway mutations for prognosis.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Shiva Bamezai, Deniz Demir, Alex Jose Pulikkottil, Fabio Ciccarone, Elena Fischbein, Amit Sinha, Chiara Borga, Geertruy te Kronnie, Lueder-Hinrich Meyer, Fabian Mohr, Maria Goetze, Paola Caiafa, Klaus-Michael Debatin, Konstanze Doehner, Hartmut Doehner, Irene Gonzalez-Menendez, Leticia Quintanilla-Fend, Tobias Herold, Irmela Jeremias, Michaela Feuring-Buske, Christian Buske, Vijay P. S. Rawat
Summary: TET1 is highly expressed in T-ALL and plays a crucial role in promoting leukemic growth by maintaining global 5-hydroxymethylcytosine (5hmC) marks to regulate cell cycle, DNA repair genes, and oncogenes. PARP enzymes participate in establishing H3K4me3 marks at the TET1 promoter and PARP inhibitor Olaparib can antagonize the growth-promoting role of TET1 in T-ALL by inducing loss of 5hmC marks.
Article
Biochemistry & Molecular Biology
Qinqin Xu, Ryan P. Mackay, Adam Y. Xiao, John A. Copland, Paul M. Weinberger
Summary: ATC is a highly lethal malignancy with no effective treatment currently available. YM155, identified as a promising candidate in a high-throughput screen, shows potential as a targeted therapy for ATC by inhibiting proliferation of cancer cells while sparing normal cells, inducing DNA damage, cell cycle arrest, and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Claire Catherinet, Diana Passaro, Stephanie Gachet, Hind Medyouf, Anne Reynaud, Charlene Lasgi, Jacques Ghysdael, Christine Tran Quang
Summary: NFAT transcription factors play crucial roles in T-ALL, essential for the development of leukemia cells. Nfat genes show functional redundancy in T-ALL and may serve as future candidate targets for therapy.
Article
Oncology
Kun-yin Qiu, Xiong-yu Liao, Zhan-wen He, Ruo-hao Wu, Yang Li, Lu-hong Xu, Dun-hua Zhou, Jian-pei Fang
Summary: The study found that ETV6/RUNX1 and BM NR were closely related to the prognosis of childhood ALL treated on COG protocols between 2000 and 2015. Additionally, a DI between 1.1 and 1.2 can serve as a significant cut-point for discriminating the risk group.
Article
Biochemistry & Molecular Biology
Rahman Ud Din, Anan Jiao, Yinxia Qiu, Aarmann Anil Mohinani Mohan, Kei-Ching Yuen, Hoi-Tung Wong, Timothy Ming-Hun Wan, Phoebe On-Yi Wong, Chun-Fung Sin
Summary: This study investigates the therapeutic efficacy of bortezomib on T-ALL and its mechanism of action. The findings suggest that bortezomib induces DNA damage and downregulates WEE1, leading to abnormal mitotic entry and mitotic catastrophe in T-ALL. This study provides insights into the use of bortezomib and the possibility of combination therapy in treating ALL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Shuang Fu, Mengqi Li, Hongtao Wang
Summary: This article describes a rare case of a 29-year-old man diagnosed with acute promyelocytic leukemia (APL) in 2019, who developed BCR-ABL1-positive acute lymphoblastic leukemia (ALL) 2 years later. The patient responded well to tyrosine kinase inhibitors and chemotherapy, achieving a molecular remission. While APL generally has a good prognosis, the prognosis of its secondary malignancies is uncertain. There are no effective measures to prevent the occurrence of secondary tumors. Increasing the frequency of laboratory testing, especially molecular biomarker monitoring, is crucial for diagnosing and treating secondary malignancies after achieving complete remission.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
Nina Richartz, Wojciech Pietka, Karin M. Gilljam, Seham Skah, Bjorn S. Skalhegg, Sampada Bhagwat, Elin Hallan Naderi, Ellen Ruud, Heidi Kiil Blomhoff
Summary: This study found that PARP1 inhibitors can enhance the effect of DNA-damaging therapy on ALL cells, providing a new treatment strategy for pediatric patients with ALL.
MOLECULAR CANCER RESEARCH
(2022)
Article
Genetics & Heredity
Constance Baer, Shunsuke Kimura, Mitra S. Rana, Andrew B. Kleist, Tim Flerlage, David J. Feith, Peter Chockley, Wencke Walter, Manja Meggendorfer, Thomas L. Olson, HeeJin Cheon, Kristine C. Olson, Aakrosh Ratan, Martha-Lena Mueller, James M. Foran, Laura J. Janke, Chunxu Qu, Shaina N. Porter, Shondra M. Pruett-Miller, Ravi C. Kalathur, Claudia Haferlach, Wolfgang Kern, Elisabeth Paietta, Paul G. Thomas, M. Madan Babu, Thomas P. Loughran, Ilaria Iacobucci, Torsten Haferlach, Charles G. Mullighan
Summary: This study reveals the hallmark of a distinct subset of chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) through somatic mutations in the chemokine gene CCL22. These mutations result in biased signaling downstream of the chemokine receptor, leading to increased cell chemotaxis and NK cell proliferation through interactions with the hematopoietic microenvironment.
Article
Hematology
Abdullah Freiwan, Jaquelyn T. Zoine, Jeremy Chase Crawford, Abishek Vaidya, Stefan A. Schattgen, Jacquelyn A. Myers, Sagar L. Patil, Mahsa Khanlari, Hiroto Inaba, Jeffery M. Klco, Charles G. Mullighan, Giedre Krenciute, Peter J. Chockley, Swati Naik, Deanna M. Lang, Maksim Mamonkin, Esther A. Obeng, Paul G. Thomas, Stephen Gottschalk, Paulina Velasquez
Summary: CD7(-) T cells can serve as a promising subset for CAR-T cell therapy of T-ALL and other hematological malignancies.
Review
Hematology
Ilaria Iacobucci, Matthew T. Witkowski, Charles G. Mullighan
Summary: Despite advances in identifying genetic drivers of ALL, prognosis for disease recurrence remains poor. Single-cell sequencing approaches are being used to explore various aspects of ALL biology, such as cell of origin, molecular heterogeneity, and interactions between leukemia cells and the microenvironment. These approaches have provided insights into gene expression, cellular differentiation, and clonal architecture in ALL, but there are still limitations to consider.
Letter
Oncology
Kentaro Ohki, Ellie R. Butler, Nobutaka Kiyokawa, Shinsuke Hirabayashi, Anke K. Bergmann, Anja Moericke, Judith M. Boer, Helene Cave, Giovanni Cazzaniga, Allen Eng Juh Yeoh, Masashi Sanada, Toshihiko Imamura, Hiroto Inaba, Charles G. Mullighan, Mignon L. Loh, Ulrika Noren-Nystrom, Lee-Yung Shih, Marketa Zaliova, Ching-Hon Pui, Oskar A. Haas, Christine J. Harrison, Anthony V. Moorman, Atsushi Manabe
Meeting Abstract
Hematology
Haley Newman, Shawn Lee, Petri Polonen, Rawan Shraim, Yimei Li, Hongyan Liu, Tiffaney L. Vincent, Richard Aplenc, Changya Chen, Zhiguo Chen, Caroline Diorio, Kimberly P. Dunsmore, Sumit Gupta, Gang Wu, Kai Tan, Meenakshi Devidas, Stuart S. Winter, Brent L. Wood, Lena E. Winestone, Jason Xu, Elizabeth A. Raetz, Mignon L. Loh, Stephen P. Hunger, Stanley B. Pounds, Kira O. Bona, Charles G. Mullighan, Jun J. Yang, David T. Teachey
Article
Hematology
David Spencer Mangum, Johnathon D. Bishop, Yinmei Zhou, Cheng Cheng, Seth E. Karol, Jeffrey E. Rubnitz, Raul C. Ribeiro, Jun J. Yang, Charles G. Mullighan, Sima Jeha, Ching-Hon Pui, Hiroto Inaba
Summary: Among children with acute lymphoblastic leukaemia, about 14.7% presented without peripheral blood blasts. While absence of blasts did not affect survival outcomes, these patients had distinct genetic and clinical characteristics, with a higher incidence of hyperdiploid B-ALL and lower rates of central nervous system involvement.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Pathology
Amy S. Duffield, Charles G. Mullighan, Michael J. Borowitz
Summary: The updated International Consensus Classification (ICC) of B-acute lymphoblastic leukemia (B-ALL) and T-acute lymphoblastic leukemia (T-ALL) includes revisions to previous subtypes and new entities. The classification incorporates recent clinical, cytogenetic, and molecular data, emphasizing whole transcriptome analysis and gene expression clustering studies. The new classification allows for improved risk stratification and optimized treatment plans for ALL patients.
Letter
Hematology
Sai Prasad Desikan, Jayastu Senapati, Elias Jabbour, Tareq Abuasab, Nicholas Short, Guilin Tang, Sa Wang, Partow Kebriaei, Tapan Kadia, Gautam Borthakur, Farhad Ravandi, Kathryn Roberts, Charles Mullighan, Marina Konopleva, Hagop Kantarjian, Nitin Jain
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Letter
Hematology
Olga K. Weinberg, Daniel A. Arber, Hartmut Doehner, Charles G. Mullighan, Etan Orgel, Anna Porwit, Richard M. Stone, Michael J. Borowitz
Letter
Oncology
N. Gossai, D. Bhojwani, E. S. Schafer, B. H. Chang, L. Pommert, A. Verma, J. Malvar, Y. Y. Chi, J. Hitzler, M. J. Burke, K. R. Rabin
Article
Oncology
Satoshi Yoshimura, John C. Panetta, Jianzhong Hu, Lie Li, Yoshihiro Gocho, Guoqing Du, Akihiro Umezawa, Seth E. Karol, Ching-Hon Pui, Charles G. Mullighan, Marina Konopleva, Wendy Stock, David T. Teachey, Nitin Jain, Jun J. Yang
Summary: LCK is a therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL), and dasatinib and ponatinib are effective inhibitors of LCK. This study evaluates the pharmacokinetics and pharmacodynamics of dasatinib and ponatinib in LCK-activated T-ALL. Both drugs demonstrate similar cytotoxic activity, with ponatinib being slightly more potent. Ponatinib exhibits slower clearance and higher exposure compared to dasatinib. Exposure-to-response models suggest that both drugs achieve significant pLCK inhibition, comparable to their effects in other leukemias. Additionally, ponatinib retains partial activity against LCK in a dasatinib-resistant T-ALL cell line model. Overall, this study provides crucial data for the development of human trials involving dasatinib and ponatinib in T-ALL.
Meeting Abstract
Oncology
L. Meyer, Ritu P. Roy, B. Huang, S. Kimura, Petri Polonen, C. Delgado-Martin, T. Vincent, T. Ryan, B. Wood, Y. Liu, J. Zhang, C. Mullighan, T. Horton, M. Loh, M. Devidas, E. Raetz, R. Hayashi, S. Winter, K. Dunsmore, S. Hunger, D. Teachey, M. Hermiston, Adam B. Olshen
Meeting Abstract
Oncology
Nicole Michmerhuizen, Bappaditya Chandra, Hazheen Shirnekhi, Swarnendu Tripathi, Brittany Pioso, David Baggett, Diana Mitrea, Ilaria Iacobucci, Michael White, Jingjing Chen, Cheon-Gil Park, Huiyun Wu, Stanley Pounds, Anna Medyukhina, Khaled Khairy, Qingsong Gao, Chunxu Qu, Scott Gorman, Simran Bawa, Carolyn Maslanka, Swati Kinger, Priyanka Dogra, Danika Di Giacomo, Cristina Mecucci, Jeffery Klco, Charles Mullighan, Richard Kriwacki
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Meeting Abstract
Biophysics
Bappaditya Chandra, Nicole Michmerhuizen, Hazheen Shirnekhi, Swarnendu Tripathi, Brittany Pioso, Anna Medyukhina, Khaled Khairy, Michael R. White, Diana M. Mitrea, Ilaria Iacobucci, Jeffery M. Klco, Charles G. Mullighan, Richard Kriwacki
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Hazheen K. Shirnekhi, Scott D. Gorman, Nicole L. Michmerhuizen, Swarnendu Tripathi, Anna Medyukhina, Khaled A. Khairy, Charles G. Mullighan, Richard W. Kriwacki
BIOPHYSICAL JOURNAL
(2022)