The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome

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The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome.

Mutations in CXCR4 cause severe leukopenia in myelokathexis or WHIM syndrome. Plerixafor inhibits binding of CXCR4 to its ligand CXCL12. We investigated the effects of plerixafor (0.04 to 0.24 mg/kg) administered at 2-4 day intervals in 6 patients. Outcome measures were the patients' complete blood cell counts, CD34(+) cell counts and lymphocyte subtypes compared with 5 normal subjects similarl...

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The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome.

WHIM syndrome is a rare congenital immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (neutropenia because of impaired egress from the BM); most patients also have severe panleukopenia. Because WHIM syndrome is caused by mutations in the chemokine receptor CXCR4 that result in increased agonist-dependent signaling, we hypothesized that the CXC...

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A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder caused by gain-of-function mutations in the G protein-coupled chemokine receptor CXCR4. The CXCR4 antagonist plerixafor, which is approved by the US Food and Drug Administration (FDA) for stem cell mobilization in cancer and administered for that indication at 0.24 mg/kg, has been sho...

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CXCR4-Specific Nanobodies as Potential Therapeutics for WHIM syndrome.

WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: warts, hypogammaglobulinemia, infections, and myelokathexis, which refers to abnormal accumulation of mature neutrophils in the bone marrow. The disease is primarily caused by C-terminal truncation mutations of the chemokine receptor CXCR4, giving these CXCR4-WHIM mutants a gain of functio...

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Regular Article CLINICAL TRIALS AND OBSERVATIONS A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor

David H. McDermott, Qian Liu, Daniel Velez, Lizbeeth Lopez, Sandra Anaya-O’Brien, Jean Ulrick, Nana Kwatemaa, Judy Starling, Thomas A. Fleisher, Debra A. Long Priel, Melissa A. Merideth, Robert L. Giuntoli, Moses O. Evbuomwan, Patricia Littel, Martha M. Marquesen, Dianne Hilligoss, Rosamma DeCastro, George J. Grimes, Samuel T. Hwang, Stefania Pittaluga, Katherine R. Calvo, Pamela Stratton, Edwa...

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ژورنال

عنوان ژورنال: Blood

سال: 2011

ISSN: 0006-4971,1528-0020

DOI: 10.1182/blood-2011-06-360586