Skip to main content

From CXCR4 mutations to WHIM syndrome

  • Chapter
Lymphocyte Trafficking in Health and Disease

Part of the book series: Progress in Inflammation Research ((PIR))

  • 515 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T (1996) Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382: 635–638

    Article  PubMed  CAS  Google Scholar 

  2. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR (1998) Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393: 595–599

    Article  PubMed  CAS  Google Scholar 

  3. Lazarini F, Tham TN, Casanova P, Arenzana-Seisdedos F, Dubois-Dalcq M (2003) Role of the alpha-chemokine stromal cell-derived factor (SDF-1) in the developing and mature central nervous system. Glia 42: 139–148

    Article  PubMed  Google Scholar 

  4. Ma Q,_ Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA (1998) Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4-and SDF-1-deficient mice. Proc Natl Acad Sci USA 95: 9448–9453

    Article  PubMed  CAS  Google Scholar 

  5. Ara T, Tokoyoda K, Sugiyama T, Egawa T, Kawabata K, Nagasawa T (2003) Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity 19: 257–267

    Article  PubMed  CAS  Google Scholar 

  6. Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, Ponomaryov T, Taichman RS, Arenzana-Seisdedos F, Fujii N et al (2002) G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 3: 687–694

    Article  PubMed  CAS  Google Scholar 

  7. Papayannopoulou T, Priestley GV, Bonig H, Nakamoto B (2003) The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization. Blood 101: 4739–4747

    Article  PubMed  CAS  Google Scholar 

  8. Liles WC, Broxmeyer HE, Rodger E, Wood B, Hubel K, Cooper S, Hangoc G, Bridger GJ, Henson GW, Calandra G et al (2003) Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 102: 2728–2730

    Article  PubMed  CAS  Google Scholar 

  9. Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, Liles WC, Li X, Graham-Evans B, Campbell TB et al (2005) Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med 201: 1307–1318

    Article  PubMed  CAS  Google Scholar 

  10. Devine SM, Flomenberg N, Vesole DH, Liesveld J, Weisdorf D, Badel K, Calandra G, Dipersio JF (2004) Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin’s lymphoma. J Clin Oncol 22: 1095–1102

    Article  PubMed  CAS  Google Scholar 

  11. Flomenberg N, Devine SM, Dipersio JF, Liesveld JL, McCarty JM, Rowley SD, Vesole DH, Badel K, Calandra G (2005) The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 106: 1867–1874

    Article  PubMed  CAS  Google Scholar 

  12. Liles WC, Rodger E, Broxmeyer HE, Dehner C, Badel K, Calandra G, Christensen J, Wood B, Price TH, Dale DC (2005) Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist. Transfusion 45: 295–300

    Article  PubMed  CAS  Google Scholar 

  13. Hernandez PA, Gorlin RJ, Lukens JN, Taniuchi S, Bohinjec J, Francois F, Klotman ME, Diaz GA (2003) Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet 34: 70–74

    Article  PubMed  CAS  Google Scholar 

  14. Gulino AV, Moratto D, Sozzani S, Cavadini P, Otero K, Tassone L, Imberti L, Pirovano S, Notarangelo LD, Soresina R et al (2004) Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome. Blood 104: 444–452

    Article  PubMed  CAS  Google Scholar 

  15. Balabanian K, Lagane B, Pablos JL, Laurent L, Planchenault T, Verola O, Lebbe C, Kerob D, Dupuy A, Hermine O et al (2004) WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12. Blood 105: 2449–2457

    Article  PubMed  CAS  Google Scholar 

  16. Kawai T, Choi U, Whiting-Theobald NL, Linton GF, Brenner S, Sechler JM, Murphy PM, Malech HL (2005) Enhanced function with decreased internalization of carboxyterminus truncated CXCR4 responsible for WHIM syndrome. Exp Hematol 33: 460–468

    Article  PubMed  CAS  Google Scholar 

  17. Haribabu B, Richardson RM, Fisher I, Sozzani S, Peiper SC, Horuk R, Ali H, Snyderman R (1997) Regulation of human chemokine receptors CXCR4. Role of phosphorylation in desensitization and internalization. J Biol Chem 272: 28726–28731

    Article  PubMed  CAS  Google Scholar 

  18. Signoret N, Rosenkilde MM, Klasse PJ, Schwartz TW, Malim MH, Hoxie JA, Marsh M (1998) Differential regulation of CXCR4 and CCR5 endocytosis. J Cell Sci 111: 2819–2830

    PubMed  CAS  Google Scholar 

  19. Signoret N, Oldridge J, Pelchen-Matthews A, Klasse PJ, Tran T, Brass LF, Rosenkilde MM, Schwartz TW, Holmes W, Dallas W et al (1997) Phorbol esters and SDF-1 induce rapid endocytosis and down modulation of the chemokine receptor CXCR4. J Cell Biol 139: 651–664

    Article  PubMed  CAS  Google Scholar 

  20. Amara A, Gall SL, Schwartz O, Salamero J, Montes M, Loetscher P, Baggiolini M, Virelizier JL, Arenzana-Seisdedos F (1997) HIV coreceptor downregulation as antiviral principle: SDF-1alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. J Exp Med 186: 139–146

    Article  PubMed  CAS  Google Scholar 

  21. Orsini MJ, Parent JL, Mundell SJ, Benovic JL, Marchese A (1999) Trafficking of the HIV coreceptor CXCR4. Role of arrestins and identification of residues in the C-terminal tail that mediate receptor internalization. J Biol Chem 274: 31076–31086

    Article  PubMed  CAS  Google Scholar 

  22. Cheng ZJ, Zhao J, Sun Y, Hu W, Wu YL, Cen B, Wu GX, Pei G (2000) Beta-arrestin differentially regulates the chemokine receptor CXCR4-mediated signaling and receptor internalization, and this implicates multiple interaction sites between beta-arrestin and CXCR4. J Biol Chem 275: 2479–2485

    Article  PubMed  CAS  Google Scholar 

  23. Babcock GJ, Farzan M, Sodroski J (2003) Ligand-independent dimerization of CXCR4, a principal HIV-1 coreceptor. J Biol Chem 278: 3378–3385

    Article  PubMed  CAS  Google Scholar 

  24. Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F (2005) The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem 280: 35760–35766

    Article  PubMed  CAS  Google Scholar 

  25. Martin C, Burdon PC, Bridger G, Gutierrez-Ramos JC, Williams TJ, Rankin SM (2003) Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 19: 583–593

    Article  PubMed  CAS  Google Scholar 

  26. Suratt BT, Petty JM, Young SK, Malcolm KC, Lieber JG, Nick JA, Gonzalo JA, Henson PM, Worthen GS (2004) Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis. Blood 104: 565–571

    Article  PubMed  CAS  Google Scholar 

  27. Lum JJ, Bren G, McClure R, Badley AD (2005) Elimination of senescent neutrophils by TNF-related apoptosis-inducing ligand. J Immunol 175: 1232–1238

    PubMed  CAS  Google Scholar 

  28. Aprikyan AA, Liles WC, Park JR, Jonas M, Chi EY, Dale DC (2000) Myelokathexis, a congenital disorder of severe neutropenia characterized by accelerated apoptosis and defective expression of bcl-x in neutrophil precursors. Blood 95: 320–327

    PubMed  CAS  Google Scholar 

  29. Wetzler M, Talpaz M, Kellagher MJ, Gutterman JU, Kurzrock R (1992) Myelokathexis: normalization of neutrophil counts and morphology by GM-CSF. JAMA 267: 2179–2180

    Article  PubMed  CAS  Google Scholar 

  30. Mentzer WC Jr, Johnston RB Jr, Baehner RL, Nathan DG (1977) An unusual form of chronic neutropenia in a father and daughter with hypogammaglobulinaemia. Br J Haematol 36: 313–322

    PubMed  Google Scholar 

  31. Zuelzer WW (1964) “Myelokathexis” — a New form of chronic granulocytopenia. Report of a case. N Engl J Med 270: 699–704

    Article  PubMed  CAS  Google Scholar 

  32. Gorlin RJ, Gelb B, Diaz GA, Lofsness KG, Pittelkow MR, Fenyk JR Jr (2000) WHIM syndrome, an autosomal dominant disorder: clinical, hematological, and molecular studies. Am J Med Genet 91: 368–376

    Article  PubMed  CAS  Google Scholar 

  33. Hess U, Ganser A, Schnurch HG, Seipelt G, Ottmann OG, Falk S, Schulz G, Hoelzer D (1992) Myelokathexis treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Br J Haematol 80: 254–256

    PubMed  CAS  Google Scholar 

  34. Arai J, Wakiguchi H, Hisakawa H, Kubota H, Kurashige T (2000) A variant of myelokathexis with hypogammaglobulinemia: lymphocytes as well as neutrophils may reverse in response to infections. Pediatr Hematol Oncol 17: 171–176

    Article  PubMed  CAS  Google Scholar 

  35. Imashuku S, Miyagawa A, Chiyonobu T, Ishida H, Yoshihara T, Teramura T, Kuriyama K, Imamura T, Hibi S, Morimoto A et al (2002) Epstein-Barr virus-associated T-lymphoproliferative disease with hemophagocytic syndrome, followed by fatal intestinal B lymphoma in a young adult female with WHIM syndrome. Warts, hypogammaglobulinemia, infections, and myelokathexis. Ann Hematol 81: 470–473

    Article  PubMed  CAS  Google Scholar 

  36. Chae KM, Ertle JO, Tharp MD (2001) B-cell lymphoma in a patient with WHIM syndrome. J Am Acad Dermatol 44: 124–128

    Article  PubMed  CAS  Google Scholar 

  37. Wetzler M, Talpaz M, Kleinerman ES, King A, Huh YO, Gutterman JU, Kurzrock R (1990) A new familial immunodeficiency disorder characterized by severe neutropenia, a defective marrow release mechanism, and hypogammaglobulinemia. Am J Med 89: 663–672

    Article  PubMed  CAS  Google Scholar 

  38. Nie Y, Waite J, Brewer F, Sunshine MJ, Littman DR, Zou YR (2004) The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity. J Exp Med 200: 1145–1156

    Article  PubMed  CAS  Google Scholar 

  39. Bowman EP, Campbell JJ, Soler D, Dong Z, Manlongat N, Picarella D, Hardy RR, Butcher EC (2000) Developmental switches in chemokine response profiles during B cell differentiation and maturation. J Exp Med 191: 1303–1318

    Article  PubMed  CAS  Google Scholar 

  40. Muehlinghaus G, Cigliano L, Huehn S, Peddinghaus A, Leyendeckers H, Hauser AE, Hiepe F, Radbruch A, Arce S, Manz RA (2005) Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells. Blood 105: 3965–3971

    Article  PubMed  CAS  Google Scholar 

  41. Krill CE Jr, Smith HD, Mauer AM (1964) Chronic idiopathic neutropenia. N Engl J Med 270: 973–979

    Article  PubMed  Google Scholar 

  42. Diaz GA (2005) CXCR4 mutations in WHIM syndrome: a misguided immune system? Immunol Rev 203: 235–243

    Article  PubMed  CAS  Google Scholar 

  43. Diaz GA, Gulino AV (2005) WHIM syndrome: a defect in CXCR4 signaling. Curr Allergy Asthma Rep 5: 350–355

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Badolato, R., Bonomi, V., Tassone, L. (2006). From CXCR4 mutations to WHIM syndrome. In: Badolato, R., Sozzani, S. (eds) Lymphocyte Trafficking in Health and Disease. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7442-X_14

Download citation

Publish with us

Policies and ethics