Article
Pediatrics
Der-Shiun Wang, Chih-Hsiang Yu, Chien-Yu Lin, Ya-Hsuan Chang, Kai-Hsin Lin, Dong-Tsamn Lin, Shiann-Tarng Jou, Meng-Yao Lu, Hsiu-Hao Chang, Shu-Wha Lin, Hsuan-Yu Chen, Yung-Li Yang
Summary: In Taiwanese children with ALL, mercaptopurine intolerance is mainly associated with NUDT15 gene variants, while patients with SUCLA2 variants receive lower doses. There is no significant difference in mean mercaptopurine doses among patients with TPMT, ITPA, MRP4, and PACSIN2 variants. NUDT15 gene variants have a clinically significant correlation with mercaptopurine intolerance.
PEDIATRIC RESEARCH
(2021)
Article
Health Care Sciences & Services
Marianne Rodrigues Fernandes, Lui Wallacy Morikawa Souza Vinagre, Juliana Carla Gomes Rodrigues, Alayde Vieira Wanderley, Sweny Marinho Fernandes, Laura Patricia Albarello Gellen, Angelica Leite de Alcantara, Beatriz Brilhante de Sousa, Rommel Mario Rodriguez Burbano, Paulo Pimentel de Assumpcao, Sidney Emanuel Batista dos Santos, Ney Pereira Carneiro dos Santos
Summary: This study investigated the correlation between genetic variants and the incidence, mortality, and prevalence rates of acute lymphoblastic leukemia (ALL). The results identified four significant genetic variants associated with the epidemiological data of ALL.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Multidisciplinary Sciences
Suvi P. M. Douglas, Atte K. Lahtinen, Jessica R. Koski, Lilli Leimi, Mikko A. Keranen, Minna Koskenvuo, Caroline A. Heckman, Kirsi Jahnukainen, Esa Pitkanen, Ulla Wartiovaara-Kautto, Outi Kilpivaara
Summary: Despite progress in ALL therapies, a significant subset of patients have poor prognosis. Research revealed that germline variants associated with predisposition to ALL are prevalent in patients, especially in adults. Acknowledging genetic factors is crucial for patient care and post-therapy follow-up.
SCIENTIFIC REPORTS
(2022)
Article
Health Care Sciences & Services
Luciana P. C. Leitao, Darlen C. de Carvalho, Juliana C. G. Rodrigues, Marianne R. Fernandes, Alayde Wanderley, Lui W. M. S. Vinagre, Natasha M. da Silva, Lucas F. Pastana, Laura P. A. Gellen, Matheus C. E. Assuncao, Sweny S. M. Fernandes, Esdras E. B. Pereira, Andre M. Ribeiro-Dos-Santos, Joao F. Guerreiro, Andrea Ribeiro-dos-Santos, Paulo P. de Assumpcao, Sidney E. B. dos Santos, Ney P. C. dos Santos
Summary: Genomic variants related to native American ancestry may increase the risk of developing Acute Lymphoblastic Leukemia (ALL). Exome analysis of Brazilian Amerindians identified six variants associated with susceptibility to ALL. These findings contribute to identifying potential genetic variants that increase the risk of ALL in Amazonian Amerindian populations and may support precision oncology measures.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Oncology
David Spencer Mangum, Julia A. Meyer, Clinton C. Mason, Soheil Shams, Luke D. Maese, Jamie D. Gardiner, Jonathan M. Downie, Deqing Pei, Cheng Cheng, Adam Gleason, Minjie Luo, Ching-Hon Pui, Richard Aplenc, Stephen P. Hunger, Mignon Loh, Mel Greaves, Nikolaus Trede, Elizabeth Raetz, J. Kimble Frazer, Charles G. Mullighan, Michael E. Engel, Rodney R. Miles, Karen R. Rabin, Joshua D. Schiffman
Summary: This study suggests that deletions in the 22q11.22 region may identify B-ALL patients with IKZF1 alterations who have very poor outcomes, offering a new genetic biomarker for risk stratification and treatment strategies. The study found that patients with combined IKZF1 alterations and 22q11.22 deletions had worse outcomes compared to patients with only IKZF1 alterations, indicating the potential significance of the 22q11.22 deletions in predicting prognosis in B-ALL patients.
Review
Oncology
Marina Oldenburg, Nadine Ruechel, Stefan Janssen, Arndt Borkhardt, Katharina L. Goessling
Summary: The concept of holobionts emphasizes the complex interactions between a host and other species, which, if disturbed may lead to disease and premature aging. The impact of chemotherapy on the microbiome and long-term dysbiosis in survivors of acute lymphoblastic leukemia requires further research.
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)
Article
Cell Biology
Yuting Zhu, Xiaopeng Ma, Heng Zhang, Yijun Wu, Meiyun Kang, Yongjun Fang, Yao Xue
Summary: The study revealed that circADD2 is down-regulated in ALL, and its overexpression inhibits cell proliferation while promoting apoptosis. circADD2 functions by directly sponging miR-149-5p.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Yao Xue, Xiaoyan Sun, Jinyu Fu, Liucheng Rong, Heng Zhang, Yuting Zhu, Xiaoyun Yang, Shaoyan Hu, Jing Chen, Yongjun Fang
Summary: Genetic variants in PI3K/Akt pathway-related miRNAs have been found to be associated with childhood acute lymphoblastic leukemia (ALL) susceptibility in the Chinese population. Specifically, the miR-149 rs2292832 mutation has a protective effect against ALL and is associated with inhibition of ALL cell proliferation and induction of apoptosis.
PEDIATRIC BLOOD & CANCER
(2023)
Review
Oncology
Ioannis Kyriakidis, Konstantinos Kyriakidis, Aspasia Tsezou
Summary: This article presents a systematic review and meta-analysis on the association between miRNA single-nucleotide polymorphisms (SNPs) and childhood acute lymphoblastic leukemia (ALL). The study identifies specific genetic variants that confer protection against ALL in children and highlights the differential expression of miRNAs in ALL. Moreover, the article explores the differences in miRNA expression patterns and signatures among different subtypes of childhood ALL.
Review
Medicine, General & Internal
Maria Kourti, Michalis Aivaliotis, Emmanouel Hatzipantelis
Summary: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and risk-directed therapy based on clinical, biologic and genetic features has played a significant role in its treatment. Despite improvement in survival rates, ALL remains a leading cause of cancer-related deaths. Proteomics is a cutting-edge technology that aims to understand the impact of the proteome on leukemia subtypes and identify new biomarkers and targets for therapy.
Article
Oncology
Marco Severgnini, Mariella D'Angio, Silvia Bungaro, Giovanni Cazzaniga, Ingrid Cifola, Grazia Fazio
Summary: In this study, RNA-seq technology was used to comprehensively profile the transcriptional landscape of childhood BCP-ALL cases. The analysis revealed a subset of conjoined genes (CGs) that were exclusively expressed in leukemic cases, suggesting a potential novel mechanism of transcriptional regulation in childhood leukemia and potential leukemia-specific biomarkers.
Article
Oncology
Soyoung Park, Ali H. Abdel Sater, Johannes F. Fahrmann, Ehsan Irajizad, Yining Cai, Hiroyuki Katayama, Jody Vykoukal, Makoto Kobayashi, Jennifer B. Dennison, Guillermo Garcia-Manero, Charles G. Mullighan, Zhaohui Gu, Marina Konopleva, Samir Hanash
Summary: This study provides evidence for the overexpression of UHRF1 in acute lymphocytic leukemia (ALL) and reveals its direct interaction with c-Myc to regulate its expression, facilitating ALL cell growth through the cMYC-CDK4/6-phosphoRb signaling pathway. Analysis of human leukemia transcriptomic datasets shows concordant overexpression of UHRF1 in B-Cell and T-Cell ALL, suggesting its potential as a therapeutic target in ALL.
Article
Clinical Neurology
Rui Li, Ji-Hong Tang, Bing-Bing Zhang, Xiao-Yan Shi, Yuan-Yuan Dai, Rui Qu
Summary: The clinical characteristics of epileptic seizures in children with acute lymphoblastic leukemia (ALL) during treatment were analyzed. Epileptic seizures mainly occurred in the induction remission period, maintenance treatment period, and after bone marrow transplantation. The common causes were MTX-related demyelinating encephalopathy and reversible posterior encephalopathy syndrome (PRES). Convulsion was the first symptom. Early neuroimaging and EEG examination are important for early diagnosis and treatment.
FRONTIERS IN NEUROLOGY
(2022)
Article
Oncology
Xiaoping Liu, Libin Huang, Ke Huang, Lihua Yang, Xu Yang, Ailing Luo, Mansi Cai, Xuedong Wu, Xiaodan Liu, Yaping Yan, Jianyun Wen, Yun Cai, Ling Xu, Hua Jiang
Summary: This study found that METTL3 gene polymorphisms were associated with increased risk of pediatric ALL, suggesting that they may be a potential biomarker for selecting ALL chemotherapeutics.
FRONTIERS IN ONCOLOGY
(2021)
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.
Article
Oncology
Hope D. Swanson, Hana Hakim, Diego R. Hijano, Ted Morton, Shane Cross, Hiroto Inaba, Sima Jeha, Ching-Hon Pui, Seth E. Karol
Summary: This study aimed to evaluate the safety of SARS-CoV-2 vaccines in patients with anti-pegaspargase antibodies. The results showed that these patients tolerated the vaccines well, which also use polyethylene glycol as a stabilizing agent, with no significant adverse reactions observed.
Article
Oncology
Andishe Attarbaschi, Anja Moericke, Christine J. Harrison, Georg Mann, Andre Baruchel, Barbara De Moerloose, Valentino Conter, Meenakshi Devidas, Sarah Elitzur, Gabriele Escherich, Stephen P. Hunger, Keizo Horibe, Atsushi Manabe, Mignon L. Loh, Rob Pieters, Kjeld Schmiegelow, Lewis B. Silverman, Jan Stary, Ajay Vora, Ching-Hon Pui, Martin Schrappe, Martin Zimmermann
Summary: This study aimed to investigate the prognostic factors and efficacy of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the first remission of patients with noninfant childhood acute lymphoblastic leukemia (ALL) with 11q23/KMT2A rearrangements. The results showed that the prognosis of patients with noninfant 11q23/KMT2A-rearranged ALL has improved compared to historical data, but allo-HSCT did not improve outcomes. Targeted therapies are needed to reduce relapse and treatment-related mortality rates.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
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
Article
Oncology
Wenting Hu, Yin Ting Cheung, Yanjing Tang, Li Hong, Yuan Zhu, Jing Chen, Zhuo Wang, Min Zhou, Yijin Gao, Jing Chen, Benshang Li, Huiliang Xue, Longjun Gu, Shuhong Shen, Jingyan Tang, Ching-Hon Pui, Hiroto Inaba, Jiaoyang Cai
Summary: Studies on the association between BMI at diagnosis and treatment outcomes in Chinese children with ALL have shown inconsistent results. While weight status was not associated with event-free survival or overall survival, overweight patients were at a higher risk of treatment-related mortality.
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)
Article
Oncology
Chih-Hsiang Yu, Shiann-Tarng Jou, Ying-Hui Su, Elane Coustan-Smith, Gang Wu, Chao-Neng Cheng, Meng-Yao Lu, Kai-Hsin Lin, Kang-Hsi Wu, Shu-Huey Chen, Fang-Liang Huang, Hsiu-Hao Chang, Jinn-Li Wang, Hsiu-Ju Yen, Meng-Ju Li, Shu-Wei Chou, Wan-Ling Ho, Yen-Lin Liu, Chia-Ching Chang, Ze-Shiang Lin, Chien-Yu Lin, Hsuan-Yu Chen, Yu-Ling Ni, Dong-Tsamn Lin, Shu-Wha Lin, Jun J. Yang, Yen-Hsuan Ni, Ching-Hon Pui, Sung-Liang Yu, Yung-Li Yang
Summary: This study analyzed data from two consecutive protocols to determine the clinical impact of minimal/measurable residual disease (MRD) and tumor genetic subtypes in newly diagnosed pediatric acute lymphoblastic leukemia (ALL) patients. The results showed that MRD-directed therapy improved outcomes for pediatric ALL, especially for standard-risk patients. This study provides important data to inform the design of future clinical trials in Taiwan.
Article
Biochemistry & Molecular Biology
Shawn H. R. Lee, Wenjian Yang, Yoshihiro Gocho, August John, Lauren Rowland, Brandon Smart, Hannah Williams, Dylan Maxwell, Jeremy Hunt, Wentao Yang, Kristine R. R. Crews, Kathryn G. G. Roberts, Sima Jeha, Cheng Cheng, Seth E. E. Karol, Mary V. V. Relling, Gary L. L. Rosner, Hiroto Inaba, Charles G. G. Mullighan, Ching-Hon Pui, William E. E. Evans, Jun J. J. Yang
Summary: Contemporary chemotherapy for childhood acute lymphoblastic leukemia is personalized based on clinical features, leukemia genomics, and minimal residual disease. However, the pharmacological basis of these prognostic variables is unclear. A study analyzing samples from 805 children with newly diagnosed leukemia identified variations in drug response and determined that certain subtypes were more sensitive to specific agents. The findings suggest opportunities for individualizing therapy and exploring alternative strategies for childhood acute lymphoblastic leukemia.
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)
Article
Hematology
Zhenhua Li, Ti-Cheng Chang, Jacob J. Junco, Meenakshi Devidas, Yizhen Li, Wenjian Yang, Xin Huang, Dale J. Hedges, Zhongshan Cheng, Mary Shago, Andrew J. Carroll, Nyla A. Heerema, Julie Gastier-Foster, Brent L. Wood, Michael J. Borowitz, Lauren Sanclemente, Elizabeth A. Raetz, Stephen P. Hunger, Eleanor Feingold, Tracie C. Rosser, Stephanie L. Sherman, Mignon L. Loh, Charles G. Mullighan, Jiyang Yu, Gang Wu, Philip J. Lupo, Karen R. Rabin, Jun J. Yang
Summary: This study investigates the genomics of Down syndrome-related acute lymphoblastic leukemia (DS-ALL) and identifies 15 molecular subtypes, as well as abnormal activation of key genes. It also reveals the common occurrence of somatic genomic abnormalities mediated by gene rearrangements in DS-ALL and the association between subtype heterogeneity and prognosis. These findings provide important insights into the biology of DS-ALL and offer opportunities for individualized treatment.
Article
Oncology
Georgios E. Christakopoulos, Kendra N. Walker, Jesse Smith, Clifford M. Takemoto, Yan Zheng, Ching-Hon Pui, Raul C. Ribeiro, Lei Wang, Stanley B. Pounds, Jeffrey E. Rubnitz, Hiroto Inaba
Summary: This study investigated the clinical management strategies and effects of cytoreduction in pediatric patients with acute myeloid leukemia (AML) and hyperleukocytosis. The results showed that LD-cytarabine treatment was safe and effective in reducing leukocyte counts in children with AML and hyperleukocytosis.
Article
Oncology
Elizabeth A. Raetz, Deepa Bhojwani, Meenakshi Devidas, Lia Gore, Karen R. Rabin, Sarah K. Tasian, David T. Teachey, Mignon L. Loh
Summary: Cure rates for acute lymphoblastic leukemia (ALL) have improved over the past decades due to intensified therapy, recognition and treatment of the central nervous system as a sanctuary site, and modern risk stratification. However, recent trials have shown that intensifying traditional chemotherapy does not provide additional benefit, indicating the need for new approaches to cure patients who have been difficult to treat. Differentiating between patients who require intensive or novel therapies and those who can be cured with minimal therapy is crucial for future trials, and new genomic biomarkers and sensitive measures of minimal/measurable residual disease offer opportunities for achieving these goals.
PEDIATRIC BLOOD & CANCER
(2023)
Letter
Oncology
Lauren K. Meyer, Ingold Huang, Benjamin J. Huang, Jong Hee Chung, Anjali Pawar, Michelle L. Hermiston, Mignon L. Loh, Robert S. Ohgami, Roberto Ruiz-Cordero, Parul Bhargava, Amanda E. Marinoff
PEDIATRIC BLOOD & CANCER
(2023)
Article
Hematology
Nathan P. Gossai, Meenakshi Devidas, Zhiguo Chen, Brent L. Wood, Patrick A. Zweidler-McKay, Karen R. Rabin, Mignon L. Loh, Elizabeth A. Raetz, Naomi J. Winick, Michael J. Burke, Andrew J. Carroll, Natia Esiashvili, Nyla A. Heerema, William L. Carroll, Stephen P. Hunger, Kimberly P. Dunsmore, Stuart S. Winter, David T. Teachey
Summary: The prognostic significance of CNS leukemic involvement in newly diagnosed T-ALL is not optimistic, and the outcomes are not affected by therapeutic differences or some treatment methods. Further research is needed to improve treatment methods.