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تسجيل

Clonal Hierarchy of Acute Myeloid Leukemia

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P947

2026-10-11

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The recognition that some mutations may be lost or acquired at relapse (e.g., FLT3-ITD), whereas others are present at diagnosis and remain stable (e.g., NPM1, PML-RARA, and CBF rearrangements) suggests that distinct clonal populations can coexist in an individual case of AML. Sequencing of serially obtained samples using bulk and single cell approaches has revealed a clonal hierarchy in AML, beginning with a founding clone that represents the initial population that becomes dominant in the bone marrow. The founding clone spawns subclones that retain founding clone mutations but gain additional mutations that confer a fitness advantage. Initial studies using bulk sequencing approaches suggested that AML evolved largely along a linear trajectory. More recent studies using single cell approaches suggest that more complex branching hierarchies are possible.

The clonal architecture of AML evolves over time as a feature of the natural history of the disease or in response to selective pressure imposed by therapy. Analysis of AML cases that entered morphologic remission after cytotoxic chemotherapy and later relapse revealed that the dominant clone at relapse retains founding clone mutations. These observations raise the hypothesis that therapies directed at eradicating drivers of the founding clone may be more effective than therapies targeting subclones.