Related Experiment Video
Updated: May 16, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
A Case Report of Tyrosine Kinase Inhibitor Interruption in a Patient with Multilineage Philadelphia-Positive Acute
Hannah Goulart1, Julie Braish2, Nicholas J Short2
1Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Introduction:
Measurable residual disease (MRD) assessment in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) commonly relies on reverse transcription polymerase chain reaction detection of BCR::ABL1 transcripts. However, discordance between BCR::ABL1 PCR and next-generation sequencing (NGS)-based MRD assays targeting immunoglobulin/T-cell receptor (IG/TR) rearrangements may occur, particularly in cases of multilineage Ph+ ALL, complicating treatment decisions such as tyrosine kinase inhibitor (TKI) discontinuation.
Case Presentation:
We report a 54-year-old female with Ph+ ALL who achieved durable remission with sustained NGS MRD negativity by IG/TR despite persistent low-level BCR::ABL1 transcript positivity. Following self-discontinuation of ponatinib, she experienced a rapid rise in BCR::ABL1 transcripts and loss of cytogenetic remission in myeloid cells, while remaining morphologically in remission and NGS MRD-negative. Reintroduction of ponatinib resulted in a prompt transcript decline.
Conclusion:
This case highlights the clinical significance of multilineage Ph+ ALL and its distinct biological background, thereby underscoring caution with TKI discontinuation despite deep NGS MRD negativity and may support continued TKI therapy in this setting.
Insights
In Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), tyrosine kinase inhibitor (TKI) discontinuation requires caution. Even with deep next-generation sequencing (NGS) negativity, persistent BCR::ABL1 transcripts signal relapse risk.
Area of Science:
- Hematology
- Oncology
- Molecular Diagnostics
Background:
- Measurable residual disease (MRD) assessment in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) typically uses BCR::ABL1 transcript detection via RT-PCR.
- Discordance between BCR::ABL1 PCR and next-generation sequencing (NGS)-based MRD assays targeting immunoglobulin/T-cell receptor (IG/TR) rearrangements can complicate treatment decisions, especially in multilineage Ph+ ALL.
- Tyrosine kinase inhibitor (TKI) discontinuation is a critical decision point influenced by MRD assessment.
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