Abstract
Although the majority of patients with chronic myeloid leukemia (CML) enjoy an excellent prognosis tyrosine kinase inhibitor (TKI) therapy, resistance remains a significant clinical problem. Resistance can arise from mutations in the kinase domain of ABL preventing drug binding, or due to ill-defined kinase-independent mechanisms. In this case report, we describe the case of a 27-year-old woman with a long-standing history of chronic phase (CP) CML who developed kinase-independent resistance with mutations in ASXL1 and RUNX1. As a consequence of uncontrolled disease, she progressed to a chronic myelomonocytic leukemia-like (CMML) accelerated phase (AP) disease with the acquisition of a mutation in IDH1. This disease progression was associated with the development of an inflammatory serositis, a phenomenon that has been described in CMML but not in AP-CML. This case presents key features of kinase-independent resistance with insight into potential mechanisms, highlights management challenges, and describes a novel systemic inflammatory response that occurred in this patient upon disease progression.
Original language | English (US) |
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Article number | 1217153 |
Journal | Frontiers in Oncology |
Volume | 13 |
DOIs | |
State | Published - 2023 |
Keywords
- ASXL1
- CML
- CMML-AP
- RUNX1
- systemic inflammatory and autoimmune diseases
- tyrosine kinase independent resistance
- tyrosine kinase inhibitors
ASJC Scopus subject areas
- Oncology
- Cancer Research