ArticleBlood advances2020
Clinical response to larotrectinib in adult Philadelphia chromosome-like ALL with cryptic ETV6-NTRK3 rearrangement.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- A genomic and epigenomic lens into the biology of acute lymphoblastic leukaemia.Nature reviews. Cancer · 2026Review
- Review
- Challenging Conventional Diagnostic Methods by Comprehensive Molecular Diagnostics: A Nationwide Prospective Comparison in Children With ALL.JCO precision oncology · 2025Article
- If it is a solid tumor target, then it may be a hematologic cancer target: Bridging the great divide.Med (New York, N.Y.) · 2025Review
- Significance and implications of FHIT gene expression and promoter hypermethylation in acute lymphoblastic leukemia (ALL).Discover oncology · 2024Article
- Advancing Diagnostics and Therapy to Reach Universal Cure in Childhood ALL.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Review
- Philadelphia-like acute lymphoblastic leukemia: the journey from molecular background to the role of bone marrow transplant-review article.Annals of hematology · 2023Review
- Chemotherapy Resistance in B-ALL with Cryptic NUP214-ABL1 Is Amenable to Kinase Inhibition and Immunotherapy.The oncologist · 2022Article
- Has Ph-like ALL Superseded Ph+ ALL as the Least Favorable Subtype?Best practice & research. Clinical haematology · 2021Review
- Twists and turns from "tumor in tumor" profiling: surveillance of chronic lymphocytic leukemia (CLL) leads to detection of a lung adenocarcinoma, whose genomic characterization alters the original hematologic diagnosis.Cold Spring Harbor molecular case studies · 2021Article
- Targeted Therapy in Acute Lymphoblastic Leukaemia.Journal of personalized medicine · 2021Review
- Genetic Alterations and Therapeutic Targeting of Philadelphia-Like Acute Lymphoblastic Leukemia.Genes · 2021Review
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
- Molecular markers in ALL: Clinical implications.Best practice & research. Clinical haematology · 2020Review
- Novel Therapies in the Treatment of Adult Acute Lymphoblastic Leukemia.Current hematologic malignancy reports · 2020Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a subtype of Ph-negative ALL that molecularly resembles Ph-positive ALL. It shares the adverse prognosis of Ph-positive ALL, but lacks the BCR-ABL1 fusion oncogene. Instead, Ph-like ALL is associated with alternative mutations in signaling pathways. We describe a case of Ph-like ALL that harbored 2 genomic alterations, which activated signaling, an NRASGly12Asp mutation, and an ETV6-NTRK3 rearrangement. Initially, the NRAS mutation was detected at high frequency, whereas the gene fusion was only detectable with a targeted next-generation sequencing-based fusion assay, but not by fluorescence in situ hybridization analysis. The disease failed to respond to multiagent chemotherapy but investigational CD19-directed chimeric antigen receptor T-cell therapy resulted in a complete remission. However, the leukemia relapsed after 6 weeks. Intriguingly, the NRAS mutation was extinguished during the chimeric antigen receptor T-cell therapy and did not contribute to the relapse, which was instead associated with a rise in ETV6-NTRK3. The relapsed leukemia progressed with further chemo- and immunotherapy but was controlled for 6 weeks with substantial leukemic cytoreduction using the TRK inhibitor larotrectinib. Unfortunately, recovery of normal hematopoiesis was only marginal and the patient eventually succumbed to infections. These results demonstrate that larotrectinib has clinical activity in ETV6-NTRK3-associated Ph-like ALL.
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