Chromothriptic cure of WHIM syndrome.

Autor: McDermott DH; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Gao JL; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Liu Q; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Siwicki M; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Martens C; Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA., Jacobs P; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Velez D; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Yim E; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Bryke CR; Quest Diagnostics, Chantilly, VA 20151, USA; Department of Cytogenetics, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Hsu N; Quest Diagnostics, Chantilly, VA 20151, USA; Department of Cytogenetics, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Dai Z; Quest Diagnostics, Chantilly, VA 20151, USA; Department of Human Genetics, Emory University School of Medicine, Decatur, GA 30030, USA., Marquesen MM; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Stregevsky E; Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Kwatemaa N; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Theobald N; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Long Priel DA; Clinical Services Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Pittaluga S; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Raffeld MA; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Calvo KR; Division of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA., Maric I; Division of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA., Desmond R; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Department of Haematology, Tallaght Hospital, Dublin 24, Ireland., Holmes KL; Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Kuhns DB; Clinical Services Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Balabanian K; INSERM UMR- S996, Laboratory of Excellence in Research on Medication and Innovative Therapeutics, Université Paris-Sud, 92140 Clamart, France., Bachelerie F; INSERM UMR- S996, Laboratory of Excellence in Research on Medication and Innovative Therapeutics, Université Paris-Sud, 92140 Clamart, France., Porcella SF; Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA., Malech HL; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Murphy PM; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pmm@nih.gov.
Jazyk: angličtina
Zdroj: Cell [Cell] 2015 Feb 12; Vol. 160 (4), pp. 686-699. Date of Electronic Publication: 2015 Feb 05.
DOI: 10.1016/j.cell.2015.01.014
Abstrakt: 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.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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