Boettcher et al report that in sibling allogeneic blood stem cell transplants, donor-derived CH expands more significantly in the recipient (orange lines) than it does in the donor (blue line), when assessed many years posttransplantation. The precise timing of the additional clonal expansion in the recipient remains unknown. One possibility is that mutant stem cells gain a transient growth advantage early after transplantation and in the context of a prevailing inflammatory environment, with growth rate reducing thereafter (upper orange line). Such behaviour has been reported in mouse models of CH. Alternatively, the recipient might continue to offer a slightly more favourable environment for the expansion of CH during and after the peri-transplant period, resulting in a persistently higher clonal growth rate (lower orange line). It is also possible that both of these alternatives operate at different times and to different extents to produce the eventual clone size observed. Future studies employing more subjects and multiple time points will be required to determine which of these scenarios prevails and the relevance to clinical outcomes. Professional illustration by Patrick Lane, ScEYEnce Studios.

Boettcher et al report that in sibling allogeneic blood stem cell transplants, donor-derived CH expands more significantly in the recipient (orange lines) than it does in the donor (blue line), when assessed many years posttransplantation. The precise timing of the additional clonal expansion in the recipient remains unknown. One possibility is that mutant stem cells gain a transient growth advantage early after transplantation and in the context of a prevailing inflammatory environment, with growth rate reducing thereafter (upper orange line). Such behaviour has been reported in mouse models of CH. Alternatively, the recipient might continue to offer a slightly more favourable environment for the expansion of CH during and after the peri-transplant period, resulting in a persistently higher clonal growth rate (lower orange line). It is also possible that both of these alternatives operate at different times and to different extents to produce the eventual clone size observed. Future studies employing more subjects and multiple time points will be required to determine which of these scenarios prevails and the relevance to clinical outcomes. Professional illustration by Patrick Lane, ScEYEnce Studios.

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