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Precursor cells of a rare leukemia tour the body to become malignant

Andrew Lane, Ludwig Cancer Research Harvard
Andrew Lane
Peter van Galen, Ludwig Cancer Research Harvard
Peter van Galen

Researchers led by Ludwig Harvard’s Andrew Lane and Peter van Galen and a couple of colleagues at the Broad Institute of MIT and Harvard reported in a June publication in Nature their analysis of the development of a leukemia that typically presents as malignant cells isolated in the skin. Sophisticated genetic and single-cell gene-expression analysis revealed that the cancer—blastic plasmacytoid dendritic cell neoplasm (BPDCN)—stems from premalignant precursors of blood cells in the bone marrow. The researchers noted that the skin tumors of BPDCN tend to show up first in places that are exposed to sunlight and bear mutations associated with UV irradiation. The UV-damage to precursor cells, however, occurs prior to the acquisition of mutations that induce malignancy. Andrew, Peter and their colleagues also captured how the precursor cells of this cancer travel between tissues to develop into a full blown malignancy. Their model proposes that precursor bone marrow cells of the cancer first accumulate mutations but largely behave normally (known as clonal hematopoiesis). Next, at least one of those cells travels to the skin and acquires more mutations from UV light. This cell subsequently acquires additional mutations to transform into a leukemic cell. The researchers also show that mutations to the Tet2 gene—found in 80% of BPDCN patients—support cell survival following exposure to UV light.

Ultraviolet radiation shapes dendritic cell leukemia transformation in the skin
Nature, 2023 June 7

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