Quantitative distribution of patient-derived leukemia clones in murine xenografts revealed by cellular barcodes

18 December 2019

In this recent study by the group of Gerald de Haan, the authors analyzed the anatomic distribution of patient-derived leukemia clones during various stages of disease progression.

https://www-nature-com.proxy-ub.rug.nl/articles/s41375-019-0695-2

Clonal heterogeneity fuels leukemia evolution, therapeutic resistance and relapse. However, it is yet unknown how leukemic clones are distributed over the body, and to what extent leukemic cells in a single anatomic site reflects the overall clonal diversity of the disease. In this recent study, we used cellular barcoding to quantitatively assess the leukemia cell content and clonal diversity in individual anatomic sites of murine xenografts. We found that the majority of leukemia cells localize in the spine and spleen, whereas the contribution of blood and pelvis, locations that are routinely assessed during clinical diagnosis and follow-up, contributed only modestly to the total body leukemia load. The absolute leukemia content in skeletal locations was directly proportional to, and limited by, the size of the location. Patient-derived leukemia clones were asymmetrically distributed across bone marrow locations. Consequently, single-site sampling of blood or pelvis resulted in substantial underestimation of the clonal heterogeneity of the disease. Altogether, our data indicate that sampling of multiple anatomic sites is required to fully capture leukemia clonal heterogeneity, and urge for clinical studies that compare the clonal distribution in human patients.