Article
Medicine, Research & Experimental
Beatriz Rosales-Rodriguez, Juan Carlos Nunez-Enriquez, Ana Claudia Velazquez-Wong, Carolina Gonzalez-Torres, Javier Gaytan-Cervantes, Elva Jimenez-Hernandez, Jorge Alfonso Martin-Trejo, Maria de los Angeles del Campo-Martinez, Aurora Medina-Sanson, Janet Flores-Lujano, Luz Victoria Flores-Villegas, Jose Gabriel Penaloza-Gonzalez, Jose Refugio Torres-Nava, Rosa Martha Espinosa-Elizondo, Raquel Amador-Sanchez, Maria Raquel Miranda-Madrazo, Jessica Denise Santillan-Juarez, Maria Luisa Perez-Saldivar, Alma Gurrola-Silva, Dario Orozco-Ruiz, Karina Anastacia Solis-Labastida, Martha Margarita Velazquez-Avina, David Aldebaran Duarte-Rodriguez, Minerva Mata-Rocha, Omar Alejandro Sepulveda-Robles, Monica Ortiz-Maganda, Vilma Carolina Bekker-Mendez, Silvia Jimenez-Morales, Juan Manuel Mejia-Arangure, Haydee Rosas-Vargas
Summary: The study investigated the association between the UKALL-CNA classifier and VER risk in Mexican children with B-ALL, finding that the intermediate and poor risk groups were significantly associated with an increased risk of VER. Even after adjusting for other factors, this risk remained significant.
ARCHIVES OF MEDICAL RESEARCH
(2021)
Article
Hematology
Sofie Gottschalk Hojfeldt, Kathrine Grell, Jonas Abrahamsson, Bendik Lund, Kim Vettenranta, Olafur G. Jonsson, Thomas L. Frandsen, Benjamin O. Wolthers, Hanne Vibeke Marquart, Goda Vaitkeviciene, Kristi Lepik, Mats Heyman, Kjeld Schmiegelow, Birgitte Klug Albertsen
Summary: Truncation of asparaginase treatment due to toxicity or silent inactivation may increase relapse risk in children with acute lymphoblastic leukemia, highlighting the importance of therapeutic drug monitoring and appropriate adjustment of therapy.
Article
Biotechnology & Applied Microbiology
Pourya Davoudi, Duy Ngoc Do, Bruce Rathgeber, Stefanie M. Colombo, Mehdi Sargolzaei, Graham Plastow, Zhiquan Wang, Karim Karimi, Guoyu Hu, Shafagh Valipour, Younes Miar
Summary: This study presents the first genome-wide CNV analysis of American mink, using whole-genome sequence data from 100 individuals. The results suggest potential links between CNVs and mink behavior, fur quality, and immune response.
Article
Oncology
Jonathan Lukas Luehmann, Marie Stelter, Marie Wolter, Josephine Kater, Jana Lentes, Anke Katharina Bergmann, Maximilian Schieck, Gudrun Goehring, Anja Moericke, Gunnar Cario, Marketa Zaliova, Martin Schrappe, Brigitte Schlegelberger, Martin Stanulla, Doris Steinemann
Summary: This study investigates the feasibility of using Optical Genome Mapping (OGM) as an all-in-one approach to determine the genetic risk profile of childhood Acute Lymphoblastic Leukemia (ALL). OGM has the potential to simplify the diagnostic workflow and identify new structural variants helpful for classifying patients into treatment groups. The results show that OGM can detect both established and new potential prognostic markers in ALL, demonstrating its promise for future diagnostic applications.
Article
Cell Biology
Yaxi Xu, Jian Hu, Wenlei Fan, Hehe Liu, Yunsheng Zhang, Zhanbao Guo, Wei Huang, Xiaolin Liu, Shuisheng Hou
Summary: This study discovered the existence of variations in the number of cervical vertebrae in duck populations. Most ducks had 15 cervical vertebrae, while a small number had 14 or 16. The number of cervical vertebrae had a positive influence on neck production, with each additional cervical vertebra resulting in an increase of 11 g or 2 cm in duck neck length. Through genome-wide analysis, six copy number variations (CNVs) associated with the number of cervical vertebrae were identified, with the associated CNV regions containing 15 genes including WNT10A and WNT6. These findings are important for understanding variations in the number of vertebrae in ducks and provide a foundation for future duck breeding.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, General & Internal
Andrej Lissat, Claudia van Schewick, Ingo G. Steffen, Ayumu Arakawa, Jean-Pierre Bourquin, Birgit Burkhardt, Guenter Henze, Georg Mann, Christina Peters, Lucie Sramkova, Cornelia Eckert, Arend von Stackelberg, Christiane Chen-Santel
Summary: The study focused on children with extramedullary relapse of acute lymphoblastic leukemia, identifying specific clinical features and poor prognosis. Individualized treatment based on patient-specific factors is necessary, and localized therapy may be beneficial in selected cases.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Genetics & Heredity
Jill Rafalko, Erica Soster, Samantha Caldwell, Eyad Almasri, Thomas Westover, Vivian Weinblatt, Philip Cacheris
Summary: This study found that genome-wide cfDNA screening can detect chromosomal abnormalities beyond traditional screening, with an overall PPV of >70% for cases with subchromosomal CNVs. Isolated CNVs had a lower PPV of 61.0% compared to complex CNVs at 93.9%. Detected abnormalities included isolated deletions/duplications and unbalanced structural rearrangements.
GENETICS IN MEDICINE
(2021)
Article
Oncology
Yoshihiro Gocho, Jingjing Liu, Jianzhong Hu, Wentao Yang, Neekesh V. Dharia, Jingliao Zhang, Hao Shi, Guoqing Du, August John, Ting-Nien Lin, Jeremy Hunt, Xin Huang, Bensheng Ju, Lauren Rowland, Lei Shi, Dylan Maxwell, Brandon Smart, Kristine R. Crews, Wenjian Yang, Kohei Hagiwara, Yingchi Zhang, Kathryn Roberts, Hong Wang, Elias Jabbour, Wendy Stock, Bartholomew Eisfelder, Elisabeth Paietta, Scott Newman, Giovanni Roti, Mark Litzow, John Easton, Jinghui Zhang, Junmin Peng, Hongbo Chi, Stanley Pounds, Mary V. Relling, Hiroto Inaba, Xiaofan Zhu, Steven Kornblau, Ching-Hon Pui, Marina Konopleva, David Teachey, Charles G. Mullighan, Kimberly Stegmaier, William E. Evans, Jiyang Yu, Jun J. Yang
Summary: The study identified LCK and BCL2 signaling as molecular determinants of dasatinib response in T-ALL patients and provided unique opportunities for targeted therapy. High BCL-XL activity, low BCL2 activity and venetoclax resistance were associated with dasatinib-sensitive T-ALL. Discordant sensitivity to dasatinib and venetoclax in T-ALL was correlated with T-cell differentiation and dynamic shift in LCK versus BCL2 activation.
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
Oncology
Hui Zhang, Anthony Pak-Yin Liu, Meenakshi Devidas, Shawn H. R. Lee, Xueyuan Cao, Deqing Pei, Michael Borowitz, Brent Wood, Julie M. Gastier-Foster, Yunfeng Dai, Elizabeth Raetz, Eric Larsen, Naomi Winick, W. Paul Bowman, Seth Karol, Wenjian Yang, Paul L. Martin, William L. Carroll, Ching-Hon Pui, Charles G. Mullighan, William E. Evans, Cheng Cheng, Stephen P. Hunger, Mary Relling, Mignon L. Loh, Jun J. Yang
Summary: The study showed that the GATA3 gene variant rs3824662 strongly influences ALL response to remission induction therapy and is associated with relapse. The findings suggest that inherited genetic variants may play a role in upfront risk stratification in ALL.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Multidisciplinary Sciences
Shaojun Zhang, Vivian Changying Jiang, Guangchun Han, Dapeng Hao, Junwei Lian, Yang Liu, Rongjia Zhang, Joseph McIntosh, Ruiping Wang, Minghao Dang, Enyu Dai, Yuanxin Wang, David Santos, Maria Badillo, Angela Leeming, Zhihong Chen, Kimberly Hartig, John Bigcal, Jia Zhou, Rashmi Kanagal-Shamanna, Chi Young Ok, Hun Lee, Raphael E. Steiner, Jianhua Zhang, Xingzhi Song, Ranjit Nair, Sairah Ahmed, Alma Rodriquez, Selvi Thirumurthi, Preetesh Jain, Nicolaus Wagner-Bartak, Holly Hill, Krystle Nomie, Christopher Flowers, Andrew Futreal, Linghua Wang, Michael Wang
Summary: This study investigates the mechanisms driving resistance to treatment in mantle cell lymphoma (MCL) by analyzing the cellular and molecular heterogeneity within patients using single-cell sequencing. The researchers found temporal activation of cancer hallmark pathways and acquisition of 17q in refractory MCL, leading to upregulation of BIRC5/survivin expression. They demonstrate that targeting BIRC5 results in effective tumor inhibition in preclinical models and also identify changes in the tumor microenvironment in refractory MCL, including decreased CD8+ T cells and aberrant cell-to-cell communication networks.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Junping Li, Lin Gao, Yusen Ye
Summary: The researchers developed a control-free method called HiSV for identifying large-scale structural variations from Hi-C samples. HiSV achieved superior accuracy and sensitivity through evaluations on simulated data sets and cancer cell lines, and effectively captured complex SVs. HiSV can also supplement the results of WGS methods.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Genetics & Heredity
Md. Panir Choudhury, Zihao Wang, Min Zhu, Shaohua Teng, Jing Yan, Shuwei Cao, Guoqiang Yi, Yuwen Liu, Yuying Liao, Zhonglin Tang
Summary: This study conducted a comprehensive analysis of copy number variations (CNVs) in different horse breeds, and identified genomic regions associated with miniature features. Functional annotation revealed the biological functions and adaptations related to these CNVs.
Article
Multidisciplinary Sciences
Qi Zhao, Feng Wang, Yan-Xing Chen, Shifu Chen, Yi-Chen Yao, Zhao-Lei Zeng, Teng-Jia Jiang, Ying-Nan Wang, Chen-Yi Wu, Ying Jing, You-Sheng Huang, Jing Zhang, Zi-Xian Wang, Ming-Ming He, Heng-Ying Pu, Zong-Jiong Mai, Qi-Nian Wu, Renwen Long, Xiaoni Zhang, Tanxiao Huang, Mingyan Xu, Miao-Zheng Qiu, Hui-Yan Luo, Yu-Hong Li, Dong-Shen Zhang, Wei-Hua Jia, Gong Chen, Pei-Rong Ding, Li-Ren Li, Zheng-Hai Lu, Zhi-Zhong Pan, Rui-Hua Xu
Summary: Through ultradeep whole-exome sequencing, we identified 46 significantly mutated genes associated with CRC and proposed a subtyping strategy that classifies CRC patients into four genomic subtypes with distinct clinical characteristics. Additionally, we found that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
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
Medicine, Research & Experimental
Davide Selvestrel, Gabriele Stocco, Marina Aloi, Serena Arrigo, Sabrina Cardile, Erika Cecchin, Mauro Congia, Debora Curci, Simona Gatti, Francesco Graziano, Carl D. Langefeld, Marianna Lucafo, Stefano Martelossi, Massimo Martinelli, Sofia Pagarin, Luca Scarallo, Elisabetta Francesca Stacul, Caterina Strisciuglio, Susan Thompson, Giovanna Zuin, Giuliana Decorti, Matteo Bramuzzo
Summary: This pharmacoepigenetic study aims to evaluate differences in DNA methylation and TPMT activity between patients with very early onset inflammatory bowel disease (VEO-IBD) and adolescents with IBD (aIBD). The study found that the DNA methylation level of cg22736354 in the TPMT gene neighborhood is lower in VEO-IBD patients, and it is associated with TPMT activity and azathioprine concentration.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
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
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
Carolin Escherich, Wenan Chen, Satoshi Miyamoto, Yui Namikawa, Wenjian Yang, David T. Teachey, Zhenhua Li, Elizabeth A. Raetz, Eric Larsen, Meenakshi Devidas, Paul L. Martin, Gang Wu, Ching-Hon Pui, Stephen P. Hunger, Mignon L. Loh, Masatoshi Takagi, Jun J. Yang
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
Pharmacology & Pharmacy
Raffaella Franca, Gabriele Stocco, Valentina Kiren, Antimo Tessitore, Franca Fagioli, Paola Quarello, Nicoletta Bertorello, Carmelo Rizzari, Antonella Colombini, Laura Rachele Bettini, Franco Locatelli, Luciana Vinti, Katia Girardi, Daniela Silvestri, Maria Grazia Valsecchi, Giuliana Decorti, Marco Rabusin
Summary: In the maintenance phase of the AIEOP-BFM ALL protocol, adjustments of mercaptopurine dosage are made based on the white blood cell count of patients. However, the concentration and variation of MP metabolites were found to have no direct impact on relapse, while children in the intermediate risk group had a higher risk of relapse. Understanding the mechanism behind the PACSIN2 rs2413739 genotype and its effect on outcomes requires further research.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Medicine, Research & Experimental
Paola Rispoli, Tatiana Scandiuzzi Piovesan, Giuliana Decorti, Gabriele Stocco, Marianna Lucafo
Summary: Induced pluripotent stem cells (iPSCs) are a promising tool for studying drug toxicities and personalized medicine. They can be differentiated into any tissue of the human body, allowing for personalized pharmacological studies and investigation of physiological differentiation processes. iPSC-derived organoids provide a more accurate representation of native organs and are useful for studying adverse drug reactions.
WIRES MECHANISMS OF DISEASE
(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.