Review
Oncology
Liwen Zhu, Wenke Bai, Qianyi Cheng, Jianpei Fang
Summary: Zinc finger protein 384 (ZNF384) is a gene that encodes a C2H2-type zinc finger protein functioning as a transcription factor. Its rearrangement has been reported in acute lymphoblastic leukemia (ALL) with more than 19 fusion partners identified. Patients with ZNF384 rearrangements in ALL generally have a favorable prognosis. The mechanisms and characteristics of different ZNF384 rearrangements in ALL have been well studied.
Article
Hematology
Marketa Zaliova, Lucie Winkowska, Jan Stuchly, Karel Fiser, Petr Triska, Martina Zwyrtkova, Ondrej Hrusak, Julia Starkova, Lucie Sramkova, Jan Stary, Jan Trka, Jan Zuna
Summary: A novel class of genetic aberration affecting the ZNF384 gene has been identified in leukemia cases, mimicking the phenotype of those with canonical ZNF384 fusions. This finding suggests that some ZNF384r-like cases represent the same genetic subtype as leukemia with canonical ZNF384 fusions.
Article
Oncology
Zhengyu Wu, Fang Zhang, Chengzhu Liu, Shuhong Shen, Jinhua Chu, Linhai Yang, Zhiwei Xie, Yu Liu, Kangkang Liu, Ningling Wang
Summary: This study reports two cases of TCF4-ZNF384 fusion in pediatric acute lymphoblastic leukemia patients, highlighting the importance of identifying ZNF384 rearrangement in ALL patients for understanding the clinical features and prognosis. Developing methods to detect ZNF384 specific translocation partners and leukemia specific targeting agents is crucial for improving the outcomes of ALL with ZNF384-rearrangement.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Xujie Zhao, Ping Wang, Jonathan D. Diedrich, Brandon Smart, Noemi Reyes, Satoshi Yoshimura, Jingliao Zhang, Wentao Yang, Kelly Barnett, Beisi Xu, Zhenhua Li, Xin Huang, Jiyang Yu, Kristine Crews, Allen Eng Juh Yeoh, Marina Konopleva, Chia-Lin Wei, Ching-Hon Pui, Daniel Savic, Jun J. Yang
Summary: FLT3 is overexpressed in ZNF384-rearranged ALL, with exclusive activation of an intergenic enhancer element at the FLT3 locus and global enrichment of active enhancers within ZNF384 binding sites. Downregulation of ZNF384 decreases FLT3 activation and sensitizes ALL cells to FLT3 inhibitor gilteritinib. Moreover, gilteritinib shows significant anti-leukemia efficacy as a monotherapy in patient-derived xenograft models of ZNF384-rearranged ALL.
NATURE COMMUNICATIONS
(2022)
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
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
Oncology
Tugce Sudutan, Yucel Erbilgin, Ozden Hatirnaz Ng, Serap Karaman, Zeynep Karakas, Fulya Kucukcankurt, Tiraje Celkan, Cetin Timur, Gul Nihal Ozdemir, Sadan Hacisalihoglu, Sema Aylan Gelen, Muge Sayitoglu
Summary: This study screened 42 MPAL and 91 BCP-ALL patients for the most common ZNF384 fusions and found a prevalence of 9.5% and 7.6% respectively. A novel breakpoint in ZNF384::TCF3 fusion was identified in one BCP-ALL patient. T-myeloid MPAL patients showed lower ZNF384 expression compared to lymphoid groups. Prognostic and patient-specific treatment evaluation of ZNF384 fusions in both ALL and MPAL might help to improve risk characterization of patients.
LEUKEMIA & LYMPHOMA
(2022)
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
Oncology
David O'Connor, Jonas Demeulemeester, Lucia Conde, Amy Kirkwood, Kent Fung, Foteini Papaleonidopoulou, Gianna Bloye, Nadine Farah, Sunniyat Rahman, Jeremy Hancock, Caroline Bateman, Sarah Inglott, Jon Mee, Javier Herrero, Peter Van Loo, Anthony V. Moorman, Ajay Vora, Marc R. Mansour
Summary: Failure to respond to induction chemotherapy is associated with poor outcome in childhood acute lymphoblastic leukemia (ALL) , especially in T-cell ALL (T-ALL). This study aimed to investigate clinical and genetic factors that influence outcome in T-ALL induction failure (IF). The study found that IF occurred in 10.3% of cases, with increasing age being a risk factor. The overall survival rate was significantly lower in IF patients compared to responsive patients. Genomic profiling revealed that TAL1 noncoding mutations were associated with poor prognosis.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Immunology
Peifang Xiao, Jiaoyang Cai, Ju Gao, Wei Gao, Xianmin Guan, Alex Wing Kwan Leung, Yiying He, Yong Zhuang, Jinhua Chu, Xiaowen Zhai, Benquan Qi, Aiguo Liu, Liangchun Yang, Jiashi Zhu, Zheng Li, Xin Tian, Yao Xue, Li Hao, Xuedong Wu, Fen Zhou, Lingzhen Wang, Jingyan Tang, Shuhong Shen, Shaoyan Hu
Summary: This study evaluated prognostic factors associated with varicella-zoster virus (VZV) infection and mortality in children with acute lymphoblastic leukemia (ALL). The results showed that patients aged >= 10 years and those with the E2A/PBX1 fusion gene had a higher incidence of VZV infection. Furthermore, VZV infection contributed to deaths in children with ALL.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Oncology
Wencke Walter, Rabia Shahswar, Anna Stengel, Manja Meggendorfer, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach
Summary: This study conducted WTS and WGS in 279 ALL patients to accurately classify genetic mutations, detect relevant genetic markers, and classify ALL patients. Through gene expression analysis, samples were classified into BCP-ALL or T-ALL group. WTS identified 97% of recurrent risk-stratifying fusions and also detected novel fusions with diagnostic potentials.
Article
Multidisciplinary Sciences
Jason P. Wray, Elitza M. Deltcheva, Charlotta Boiers, Jyoti Bikram Chhetri, John Brown, Sladjana Gagrica, Yanping Guo, Anuradha Illendula, Joost H. A. Martens, Hendrik G. Stunnenberg, John H. Bushweller, Rachael Nimmo, Tariq Enver, Simon E. Richardson
Summary: This study characterizes the ETV6-RUNX1 regulome and reveals its functional antagonism with native RUNX1 in pediatric B-ALL. The authors show that ETV6-RUNX1 primarily functions through competing for RUNX1 binding sites and transcriptional repression. They also demonstrate the sustained requirement for RUNX1 activity in leukemia cells and suggest the therapeutic potential of targeting the RUNX1 program in ALL.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Na Lin, Xiaojing Yan, Dali Cai, Lei Wang
Summary: ZNF384 rearrangements are common in both B-ALL and B/M MPAL, with a tendency towards lineage conversion. TCF3-ZNF384 fusion is associated with poor steroid response and high relapse rates, mainly seen in children and adolescents.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Thomas Burmeister, Daniela Groeger, Nicola Goekbuget, Bernd Spriewald, Michael Starck, Ahmet Elmaagacli, Dieter Hoelzer, Ulrich Keller, Stefan Schwartz
Summary: The translocation t(1;19)(q23;p13) with the resulting chimeric TCF3::PBX1 gene is the third most prevalent recurrent chromosomal translocation in acute lymphoblastic leukemia. This study provides extensive molecular data on the chromosomal breakpoints of this translocation in adult patients and explores the feasibility of using patient-specific chromosomal break sites as molecular markers for detecting measurable residual disease (MRD). A highly sensitive generic real-time PCR for MRD assessment using these breakpoint sequences was established, offering a potential alternative to the classical method utilizing rearranged immune gene loci.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Yizhen Li, Wentao Yang, Meenakshi Devidas, Stuart S. Winter, Chimene Kesserwan, Wenjian Yang, Kimberly P. Dunsmore, Colton Smith, Maoxiang Qian, Xujie Zhao, Ranran Zhang, Julie M. Gastier-Foster, Elizabeth A. Raetz, William L. Carroll, Chunliang Li, Paul P. Liu, Karen R. Rabin, Takaomi Sanda, Charles G. Mullighan, Kim E. Nichols, William E. Evans, Ching-Hon Pui, Stephen P. Hunger, David T. Teachey, Mary Relling, Mignon L. Loh, Jun J. Yang
Summary: Genetic alterations in the RUNX1 gene are associated with various blood disorders, especially those of the megakaryocyte and myeloid lineages. Germline RUNX1 variants have different effects on B-ALL and T-ALL, with the latter showing severe damaging effects. Additionally, JAK3 mutation is a common somatic genomic abnormality in T-ALL with germline RUNX1 variants.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
