Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Purpose: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear.
Methods: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. We evaluated the effect of age-related gene expression signature on ALL treatment outcomes.
Results: Seven ALL drugs (asparaginase, prednisolone, mercaptopurine, dasatinib, nelarabine, daunorubicin, and inotuzumab ozogamicin) showed differential activity between children and adults, of which six were explained by age-related differences in leukemia molecular subtypes. Adolescents and young adults showed similar patterns of drug resistance as older adults, relative to young children. Mercaptopurine exhibited subtype-independent greater sensitivity in children. Transcriptomic profiling uncovered subclusters within -, -, and -rearranged ALL that were linked to age and cytotoxic drug resistance. In particular, a subset of children had adult-like ALL on the basis of leukemia gene expression patterns across subtypes, despite their chronological age. Resistant to cytotoxic drugs, children with adult-like ALL exhibited poor prognosis in pediatric ALL trials, even after adjusting for age and minimal residual diseases.
Conclusion: Our results provide pharmacogenomic insights into age-related disparities in ALL cure rates and identify leukemia prognostic features for treatment individualization across age groups.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458355 | PMC |
| http://dx.doi.org/10.1200/JCO.24.00500 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel Prognostic Scoring Systems for Severe CRS after Anti-CD19 CAR-T-Cells in Acute B-Lymphoblastic Leukemia.
Curr Med Sci
September 2025
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Objective: To develop a novel prognostic scoring system for severe cytokine release syndrome (CRS) in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with anti-CD19 chimeric antigen receptor (CAR)-T-cell therapy, aiming to optimize risk mitigation strategies and improve clinical management.
Methods: This single-center retrospective cohort study included 125 B-ALL patients who received anti-CD19 CAR-T-cell therapy from January 2017 to October 2023. These cases were selected from a cohort of over 500 treated patients on the basis of the availability of comprehensive baseline data, documented CRS grading, and at least 3 months of follow-up.
Serum SERS Analysis Reveals Amino Acid- and Protein-Associated Vibrational Features for Subtype Identification in Acute Lymphoblastic Leukemia.
Anal Chem
September 2025
Department of Laboratory Medicine, Fujian Medical University, Fuzhou 350004, China.
Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. Current clinical diagnosis primarily relies on invasive detection methods, while molecular subtyping remains a complex and time-consuming process. This study innovatively employed silver nanoparticle-based surface-enhanced Raman spectroscopy (SERS) technology to systematically analyze 116 serum samples, including those with breakpoint cluster region-Abelson (-) fusion genotype, mixed-lineage leukemia (, also known as lysine methyltransferase 2A, ) gene rearrangement subtype, T-lymphoblastic ALL, and healthy controls.
View Article and Find Full Text PDFLineage Switch of Adult B-Cell Acute Lymphoblastic Leukaemia to Acute Myeloid Leukaemia Following B-Cell-Directed Therapy.
Eur J Case Rep Intern Med
August 2025
Division of Hematology and Oncology, UNM Comprehensive Cancer Center, Albuquerque, USA.
Background: Blinatumomab and inotuzumab ozogamicin (InO) are B-cell targeted agents used in the frontline and relapsed/refractory treatment of B-cell acute lymphoblastic leukaemia (B-ALL). Blinatumomab, a bispecific T-cell engager that targets CD19 and CD3, and InO, an antibody-drug conjugate targeting CD22, have both shown efficacy. However, recent reports have noted lineage conversion as a complication when these agents are used individually or sequentially.
View Article and Find Full Text PDFSuccessful remission induction therapy with azacitidine and venetoclax for a treatment-naive elderly patient with ETP/myeloid mixed-phenotype acute leukemia: a case report.
Front Oncol
August 2025
Department Hematopathology, Shenzhen Hospital of Southern Medical University, Shenzhen, China.
Background: Mixed-phenotype acute leukemia (MPAL) is a rare acute leukemia for which data are currently not available to guide therapy. It has a poor outcome, particularly in elderly patients.
Case Presentation: We report the successful use of venetoclax/azacitidine as treatment for a treatment-naive elderly patient with early T-cell precursor (ETP)/myeloid MPAL.
A Rare Case of F-FDG-avid Renomegaly as the Initial Presentation of Acute Lymphoblastic Leukemia.
Indian J Nucl Med
August 2025
Department of Nuclear Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India.
Acute lymphoblastic leukaemia (ALL) is a prevalent cause of paediatric leukaemia. Patients with ALL typically exhibit symptoms such as fever, bleeding, weight loss, and bone pain. Blood investigations results predominantly show anaemia and pancytopenia with blast cells in the peripheral smear.
View Article and Find Full Text PDF