At ASH 2025, Richard Van Etten, MD, PhD, shared paradigm-shifting findings from the UCI Center for Cancer Systems Biology that reconsider how chronic myeloid leukemia (CML) develops at its earliest stages.

For decades, CML has been viewed as a disease driven solely by a defining chromosomal translocation that creates a single oncogene. Van Etten’s work demonstrates that while this mutation is necessary, it is not sufficient on its own. Using a preclinical mouse model, the research shows that low levels of hematopoietic stem cells carrying the oncogene can persist without progressing to leukemia. Disease development occurs only once a critical threshold of malignant stem cells accumulates within the bone marrow.

This threshold-based model aligns with emerging evidence across multiple cancer types, where normal tissues can harbor cancer-associated “driver” mutations without advancing to malignancy. The findings offer a more nuanced understanding of leukemogenesis and open new avenues for thinking about early disease biology, risk stratification, and intervention timing.

The work highlights how systems biology approaches at UC Irvine are reshaping foundational assumptions in hematologic malignancies, and helping redefine what truly drives cancer progression.