ArticleOncotarget2016
Prognostic and therapeutic role of targetable lesions in B-lineage acute lymphoblastic leukemia without recurrent fusion genes.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- The clinical relevance of RAS pathway gene mutations in childhood B-cell acute lymphoblastic leukemia.Annals of hematology · 2026Article
- Novel molecular mechanisms of FLT3 deregulation: from the acute myeloid leukemia experience to therapeutic insights in acute lymphoblastic leukemia.Molecular cancer · 2025Review
- A rare case of B-cell acute lymphoblastic leukemia with translocation (14;14)(q11.2;q32) involving IGH and CEBPE with review of the literature.Journal of hematopathology · 2025Review
- Discovery of Cis-Regulatory Mechanisms via Non-Coding Mutations in Acute Lymphoblastic Leukemia.Genes, chromosomes & cancer · 2025Article
- Preferential Genetic Pathways Lead to Relapses in Adult B-Cell Acute Lymphoblastic Leukemia.Cancers · 2024Article
- The advances of E2A-PBX1 fusion in B-cell acute lymphoblastic Leukaemia.Annals of hematology · 2024Review
- A case report of secondary B-cell acute lymphoblastic leukemia treated with a combination of FLT3 inhibitor and decitabine.Frontiers in oncology · 2024Article
- Added value of molecular karyotype in childhood acute lymphoblastic leukemia.Cancer innovation · 2023Article
- The Genomic Landscape of a Restricted ALL Cohort from Patients Residing on the U.S./Mexico Border.International journal of environmental research and public health · 2021Article
- Article
- A phase I study of a dual PI3-kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia.BMC pharmacology & toxicology · 2020Article
- Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients.Journal of personalized medicine · 2020Article
- Resistance of t(17;19)-acute lymphoblastic leukemia cell lines to multiagents in induction therapy.Cancer medicine · 2019Article
- Next-Generation Sequencing in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2019Review
- Prognostic implications of additional genomic lesions in adult Philadelphia chromosome-positive acute lymphoblastic leukemia.Haematologica · 2019Article
- Biological Aspects of mTOR in Leukemia.International journal of molecular sciences · 2018Review
- Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications.British journal of haematology · 2018Article
- RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications.Haematologica · 2016Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
To shed light into the molecular bases of B-lineage acute lymphoblastic leukemia lacking known fusion transcripts, i.e. BCR-ABL1, ETV6-RUNX1, E2A-PBX1, and MLL rearrangements (B-NEG ALL) and the differences between children, adolescents/young adults (AYA) and adults, we analyzed 168 B-NEG ALLs by genome-wide technologies. This approach showed that B-NEG cases carry 10.5 mutations and 9.1 copy-number aberrations/sample. The most frequently mutated druggable pathways were those pertaining to RAS/RTK (26.8%) and JAK/STAT (12.5%) signaling. In particular, FLT3 and JAK/STAT mutations were detected mainly in AYA and adults, while KRAS and NRAS mutations were more frequent in children. RAS/RTK mutations negatively affected the outcome of AYA and adults, but not that of children. Furthermore, adult B-NEG ALL carrying JAK/STAT mutations had a shorter survival. In vitro experiments showed that FLT3 inhibitors reduced significantly the proliferation of FLT3-mutated primary B-NEG ALL cells. Likewise, PI3K/mTOR inhibitors reduced the proliferation of primary cells harboring RAS and IL7R mutations. These results refine the genetic landscape of B-NEG ALL and suggest that the different distribution of lesions and their prognostic impact might sustain the diverse outcome between children, adults and partly AYA - whose genomic scenario is similar to adults - and open the way to targeted therapeutic strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.