Mohamad Mohty, Head of the Clinical Hematology and Cellular Therapy Department at Saint-Antoine Hospital, Sorbonne University, shared on LinkedIn:
“Could acute myeloid leukemia (AML) begin 50 years before diagnosis?
Just finished reading this fascinating new study published in Nature by Watson and colleagues. It definitely challenges our understanding of how acute myeloid leukemia (AML) develops.
Using longitudinal blood samples and ultra-sensitive sequencing, the investigators reconstructed the evolutionary history of preleukemic clones.
I can identify 3 key findings:
- Leukemia may begin remarkably early: in approximately two-thirds of future AML patients, the first driver mutation was estimated to have occurred before age 20!
- Clonal evolution progressively accelerates: as additional driver mutations accumulate, the selective advantage of preleukemic clones increases dramatically, sometimes allowing them to double within weeks or months.
- Clonal dominance matters: large somatic clonal expansions were associated with a strikingly increased risk of subsequent myeloid malignancy (OR 107 in an independent UK Biobank analysis).
The implications are profound. Perhaps the future of AML risk prediction will depend not only on identifying mutations, but also on understanding their evolutionary dynamics, clonal competition, and growth trajectories. Could we eventually identify high-risk clones decades before leukemia develops and intervene before malignant transformation?
Of course, clinical validation and prospective intervention studies remain essential, but we need to move beyond a static snapshot of clonal hematopoiesis and start understanding the entire movie of its evolution. Because the future of leukemia «prevention» may lie in changing the trajectory of clonal evolution before it becomes irreversible.”
Title: Evolutionary dynamics in the years preceding acute myeloid leukaemia
Authors: Caroline J. Watson, Gladys Y. P. Poon, Hamish A. J. MacGregor, Adriana V. A. Fonseca, Sophia Apostolidou, Aristi Damaskou, Christopher Boniface, Samuel Hackett, Aleksandra Gentry-Maharaj, Usha Menon, Jamie R. Blundell
Read the Full Article on Nature
You can also read: Time Toxicity in Acute Myeloid Leukemia Care and the Potential of All-Oral Therapy
