Pillole: per capire
Neutropenia da mielocatessi
NEUTROPENIA DUE TO MYELOKATHEXIS
Raffaele Badolato
Clinica Pediatrica, Università di Brescia
Gennaio 2009 - pagg. 35 -38
Abstract
The works describes a case of WHIM (Warts, Hypogammaglobulinemia, Immunodeficit,
Myelokathexis) characterized by neutropenia, hypogammaglobulinemia, reduced number
of lymphocytes B (C19) in blood stream, and bone marrow rich in element of the myeloid
series. The syndrome is due to a mutation of the receptor CXCR4 present both in the myeloid
cells and in the limphocytes B for the ligand SDF1 placed on the stromal cells of the
bone marrow and in the lymphatic tissue. The expression of the mutant receptor in neutrophyles
and in the plasma cells does not stop with cell maturation, thus causing a protracted
adhesion of the mature cells to the marrow stroma and lymphatic organs, with consequent
myelokathexis, neutropenia and hypogammaglobulinemia.
Classificazione MeSH
Bibliografia
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Kawabata K, Nagasawa T. Long-term hematopoietic
stem cells require stromal cell-derived
factor-1 for colonizing bone marrow during
ontogeny. Immunity 2003;19:257-67.
• Balabanian K, Lagane B, Pablos JL. WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitisation to CXCL12. Blood 2005;105:2449-57.
• Diaz GA. CXCR4 mutations in WHIM syndrome: a misguided immune system? Immunol Rev 2005;203:235-43.
• Futahashi Y, Komano J, Urano E. Separate elements are required for ligand-dependent and -independent internalisation of metastatic potentiator CXCR4. Cancer Sci 2007;98:373-9.
• Gorlin RJ, Gelb B, Diaz GA, Lofsness KG, Pittelkow MR, Fenyk JR Jr. WHIM syndrome, an autosomal dominant disorder: clinical, hematological, and molecular studies. Am J Med Genet 2000;91:368-76.
• Gulino AV, Moratto D, Sozzani S, et al. Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome. Blood 02004;104:444-52.
• Haribabu B, Richardson RM, Fisher I, et al. Regulation of human chemokine receptors CXCR4. Role of phosphorylation in desensitisation and internalisation. J Biol Chem 1997; 272:28726-31.
• Hernandez PA, Gorlin RJ, Lukens JN, et al. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet 2003;34:70-4.
• Kawai T, Choi U, Whiting-Theobald NL, et al. Enhanced function with decreased internalisation of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome. Exp Hematol 2005;33:460-8.
•Ma Q, Jones D, Borghesani PR. Impaired Blymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 1998;95:9448-53.
•Mentzer WC Jr, Johnston RB Jr, Baehner RL, Nathan DG. An unusual form of chronic neutropenia in a father and daughter with hypogammaglobulinaemia. Br J Haematol 1977;36: 313-22.
• Nagasawa T, Hirota S, Tachibana K. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 1996;382:635-8.
• Papayannopoulou T, Priestley GV, Bonig H, Nakamoto B. The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization. Blood 2003;101:4739-47.
• Petit I, Szyper-Kravitz M, Nagler A. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 2002;3:687-94.
• Sallusto F, Mackay CR, Lanzavecchia A. The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol 2000;18:593-620.
• Viola A, Contento RL, Molon B. T cells and their partners: The chemokine dating agency. Trends Immunol 2006;27;421-27.
• Zhang Y, Foudi A, Geay JF. Intracellular localization and constitutive endocytosis of CXCR4 in human CD34+ hematopoietic progenitor cells. Stem Cells 2004;22:1015-29.
• Zuelzer WW. “Myelokathexis” - A new form of chronic granulocytopenia. Report of a Case. N Engl J Med 1964;270:699-704.
• Balabanian K, Lagane B, Pablos JL. WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitisation to CXCL12. Blood 2005;105:2449-57.
• Diaz GA. CXCR4 mutations in WHIM syndrome: a misguided immune system? Immunol Rev 2005;203:235-43.
• Futahashi Y, Komano J, Urano E. Separate elements are required for ligand-dependent and -independent internalisation of metastatic potentiator CXCR4. Cancer Sci 2007;98:373-9.
• Gorlin RJ, Gelb B, Diaz GA, Lofsness KG, Pittelkow MR, Fenyk JR Jr. WHIM syndrome, an autosomal dominant disorder: clinical, hematological, and molecular studies. Am J Med Genet 2000;91:368-76.
• Gulino AV, Moratto D, Sozzani S, et al. Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome. Blood 02004;104:444-52.
• Haribabu B, Richardson RM, Fisher I, et al. Regulation of human chemokine receptors CXCR4. Role of phosphorylation in desensitisation and internalisation. J Biol Chem 1997; 272:28726-31.
• Hernandez PA, Gorlin RJ, Lukens JN, et al. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet 2003;34:70-4.
• Kawai T, Choi U, Whiting-Theobald NL, et al. Enhanced function with decreased internalisation of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome. Exp Hematol 2005;33:460-8.
•Ma Q, Jones D, Borghesani PR. Impaired Blymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 1998;95:9448-53.
•Mentzer WC Jr, Johnston RB Jr, Baehner RL, Nathan DG. An unusual form of chronic neutropenia in a father and daughter with hypogammaglobulinaemia. Br J Haematol 1977;36: 313-22.
• Nagasawa T, Hirota S, Tachibana K. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 1996;382:635-8.
• Papayannopoulou T, Priestley GV, Bonig H, Nakamoto B. The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization. Blood 2003;101:4739-47.
• Petit I, Szyper-Kravitz M, Nagler A. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 2002;3:687-94.
• Sallusto F, Mackay CR, Lanzavecchia A. The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol 2000;18:593-620.
• Viola A, Contento RL, Molon B. T cells and their partners: The chemokine dating agency. Trends Immunol 2006;27;421-27.
• Zhang Y, Foudi A, Geay JF. Intracellular localization and constitutive endocytosis of CXCR4 in human CD34+ hematopoietic progenitor cells. Stem Cells 2004;22:1015-29.
• Zuelzer WW. “Myelokathexis” - A new form of chronic granulocytopenia. Report of a Case. N Engl J Med 1964;270:699-704.
Corrispondenza: badolato@med.unibs.it