| First Author | McDermott DH | Year | 2015 |
| Journal | Cell | Volume | 160 |
| Issue | 4 | Pages | 686-99 |
| PubMed ID | 25662009 | Mgi Jnum | J:219886 |
| Mgi Id | MGI:5629905 | Doi | 10.1016/j.cell.2015.01.014 |
| Citation | McDermott DH, et al. (2015) Chromothriptic cure of WHIM syndrome. Cell 160(4):686-99 |
| abstractText | Chromothripsis is a catastrophic cellular event recently described in cancer in which chromosomes undergo massive deletion and rearrangement. Here, we report a case in which chromothripsis spontaneously cured a patient with WHIM syndrome, an autosomal dominant combined immunodeficiency disease caused by gain-of-function mutation of the chemokine receptor CXCR4. In this patient, deletion of the disease allele, CXCR4(R334X), as well as 163 other genes from one copy of chromosome 2 occurred in a hematopoietic stem cell (HSC) that repopulated the myeloid but not the lymphoid lineage. In competitive mouse bone marrow (BM) transplantation experiments, Cxcr4 haploinsufficiency was sufficient to confer a strong long-term engraftment advantage of donor BM over BM from either wild-type or WHIM syndrome model mice, suggesting a potential mechanism for the patient's cure. Our findings suggest that partial inactivation of CXCR4 may have general utility as a strategy to promote HSC engraftment in transplantation. |
