PS01 ONCO-17

Transition points in chronic myeloid leukemia progression and treatment

Monday, July 14 at 6:00pm in

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Jonathan Rodriguez

University of California, Irvine
"Transition points in chronic myeloid leukemia progression and treatment"
Chronic myeloid leukemia (CML) is a blood cancer characterized by dysregulated production of maturing myeloid cells driven by the product of the Philadelphia chromosome, the BCR::ABL1 tyrosine kinase. Tyrosine kinase inhibitors (TKI) have proved effective in treating CML but there is still a cohort of patients who do not respond to TKI therapy even in the absence of mutations in the BCR::ABL1 kinase domain that mediate drug resistance. Recent experiments reveal that interactions and competition between different cellular compartments and between normal and BCR::ABL1-expressing cells form a threshold that determines whether the malignant cells can expand and cause leukemia. To discover novel strategies to improve TKI therapy in CML and identify the mechanisms behind the threshold, we developed a nonlinear mathematical model of CML hematopoiesis that incorporates feedback control and parallel lineages. Cell-cell interactions were constrained with insights from an automated model selection method together with previous observations and in vivo data from a chimeric BCR::ABL1 transgenic mouse model of CML. The resulting quantitative model captures the dynamics of normal and CML cells at various stages of the disease, exhibits variable responses to TKI treatment, and predicts key factors of transitional points of disease progression.



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Annual Meeting for the Society for Mathematical Biology, 2025.