Is hematopoietic stem cell homing deficient in Fanconi anemia?
To the editor: We read with interest the article by Zhang and colleagues comparing progenitor colony formation, chimerism after xenotransplantation into immunodeficient mice, and adhesive properties of whole bone marrow (WBM) cells from Fanconi anemia (FA) patients and healthy donors.1 We applaud the study of this important topic, but would caution that assays of clonogenicity and hematopoietic repopulation are not sufficiently specific measures of homing. In fact, both are inherently skewed by the complex phenotype of FA hematopoietic stem cells (HSCs), comprising exaggerated apoptotic responses, constitutive cell-cycle arrest, pronounced sensitivity to reactive oxygen species, and reduced replicative fitness.2,3 Furthermore, the ability of cells to home to the microenvironment is an attribute of primitive cells. Experimental observations in WBM cells or immortalized lymphoblasts are not always faithful reflections of stem and progenitor cell behavior.4 For example, the expression of
