Unknown

Dataset Information

0

Chromothriptic cure of WHIM syndrome.


ABSTRACT: 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.

SUBMITTER: McDermott DH 

PROVIDER: S-EPMC4329071 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 he  ...[more]

Similar Datasets

| S-EPMC6698215 | biostudies-literature
| S-EPMC4588533 | biostudies-literature
| S-EPMC6337672 | biostudies-literature
| S-EPMC5743603 | biostudies-literature
| S-EPMC6425947 | biostudies-literature
| S-EPMC10097661 | biostudies-literature
| S-EPMC9519442 | biostudies-literature
| S-EPMC5648064 | biostudies-literature
| S-EPMC6587139 | biostudies-literature
| S-EPMC8821066 | biostudies-literature