ArticleHaematologica2011
Philadelphia-positive acute lymphoblastic leukemia patients already harbor BCR-ABL kinase domain mutations at low levels at the time of diagnosis.
Article in Haematologica, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 92 citations in OpenAlex.
- Preferential Genetic Pathways Lead to Relapses in Adult B-Cell Acute Lymphoblastic Leukemia.Cancers · 2024Article
- New ABL1 Kinase Domain Mutations in BCR::ABL1-Positive Acute Lymphoblastic Leukemia.Cancer medicine · 2024Article
- Asciminib antagonizes transplantable BCR::ABL1-positive lymphoid blast crisis in vivo by targeting malignant stem cells.Leukemia · 2024Article
- Tyrosine kinase inhibitor resistance in de novo BCR::ABL1-positive BCP-ALL beyond kinase domain mutations.Blood advances · 2024Article
- Review
- How to Manage Philadelphia-Positive Acute Lymphoblastic Leukemia in Resource-Constrained Settings.Cancers · 2023Review
- Ph+ ALL in 2022: is there an optimal approach?Hematology. American Society of Hematology. Education Program · 2022Article
- Article
- Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA.Scientific reports · 2022Article
- Digital Droplet PCR in Hematologic Malignancies: A New Useful Molecular Tool.Diagnostics (Basel, Switzerland) · 2022Review
- INCB84344-201: Ponatinib and steroids in frontline therapy for unfit patients with Ph+ acute lymphoblastic leukemia.Blood advances · 2022Article
- Detection ofHaematologica · 2022Article
- Article
- Current Management and New Developments in the Treatment of ALL.Cancer treatment and research · 2021Article
- Article
- Impact of TKIs post-allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive ALL.Blood · 2020Article
- Next-generation sequencing for BCR-ABL1 kinase domain mutations in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A position paper.Cancer medicine · 2020Review
- Practical guidance for the management of acute lymphoblastic leukemia in the adolescent and young adult population.Therapeutic advances in hematology · 2020Review
- Curing Ph+ ALL: assessing the relative contributions of chemotherapy, TKIs, and allogeneic stem cell transplant.Hematology. American Society of Hematology. Education Program · 2019Article
- Tyrosine kinase inhibitor prophylaxis after transplant for Philadelphia chromosome-positive acute lymphoblastic leukemia.Cancer science · 2019Article
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn patients with Philadelphia-positive acute lymphoblastic leukemia, resistance to treatment with tyrosine kinase inhibitors is frequent and most often associated with the development of point mutations in the BCR-ABL kinase domain. We aimed to assess: (i) in how many patients BCR-ABL kinase domain mutations are already detectable at relatively low levels at the time of diagnosis, and (ii) whether mutation detection correlates with subsequent response to therapy. DESIGN AND
methodsWe retrospectively analyzed samples collected at diagnosis from 15 patients with Philadelphia-positive acute lymphoblastic leukemia who subsequently received tyrosine kinase inhibitor therapy (dasatinib) by cloning the BCR-ABL kinase domain in a bacterial vector and sequencing 200 independent clones per sample.
resultsMutations at relatively low levels (2-4 clones out of 200) could be detected in all patients--eight who relapsed and seven who achieved persistent remission. Each patient had evidence of two to eight different mutations, the majority of which have never been reported in association with resistance to tyrosine kinase inhibitors. In two patients out of six who relapsed because of a mutation, the mutation (a T315I) was already detectable in a few clones at the time of diagnosis. On the other hand, a patient who was found to harbor an F317L mutation is in persistent remission on dasatinib.
conclusionsOur results suggest that the BCR-ABL kinase domain is prone to randomly accumulate point mutations in Philadelphia-positive acute lymphoblastic leukemia, although the presence of these mutations in a relatively small leukemic subclone does not always preclude a primary response to tyrosine kinase inhibitors.
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