Experimental Hematology
Volume 37, Issue 1 , Pages 1-7 , January 2009

Thrombocytopenia with absent radii (TAR) syndrome: from hemopoietic progenitor to mesenchymal stromal cell disease?

  • Laura Bonsi

      Affiliations

    • Departments of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy
    • Drs. Bonsi and Marchionni contributed equally to this article.
    • ,
  • Cosetta Marchionni

      Affiliations

    • Departments of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy
    • Drs. Bonsi and Marchionni contributed equally to this article.
    • ,
  • Francesco Alviano

      Affiliations

    • Departments of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy
    • ,
  • Giacomo Lanzoni

      Affiliations

    • Departments of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy
    • ,
  • Michele Franchina

      Affiliations

    • Obstetrics and Gynecology, University of Bologna, Bologna, Italy
    • ,
  • Roberta Costa

      Affiliations

    • Departments of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy
    • ,
  • Alberto Grossi

      Affiliations

    • Departments of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy
    • ,
  • Gian Paolo Bagnara

      Affiliations

    • Departments of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy
    • “Giorgio Prodi” Interdepartmental Center for Cancer Research, University of Bologna, Bologna, Italy
    • Corresponding Author InformationOffprint requests to: Gian Paolo Bagnara, M.D., Department of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro, 840126 Bologna, Italy

Received 25 July 2008 ,Revised 3 September 2008 ,Accepted 4 September 2008.

References 

  1. Bernhard WG, Gore I, Kilby RA. Congenital leukemia. Blood. 1951;6:990–1001
  2. Hall JG, Levin J, Kuhn JP. Thrombocytopenia with absent radius. Medicine. 1969;18:411–439
  3. Edelberg S, Cohn J, Brandt N. Congenital hypomegakaryocytic thrombocytopenia associated with bilateral absence of radius-the TAR syndrome: intra-family variation of the clinical picture. Hum Hered. 1977;27:147–152
  4. Hedberg VA, Lipton JM. Thrombocytopenia with absent radii. A review of 100 cases. Am J Pediatr Hematol Oncol. 1988;10:51–64
  5. Urban M, Opitz C, Bommer C, Enders H, Tinschert S, Witkowski R. Bilaterally cleft lip, limb defects, and haematological manifestations: Roberts syndrome versus TAR syndrome. Am J Med Genet. 1998;79:155–160
  6. Alter B, Young N. The bone marrow failure syndrome. In:  Nathan D,  Oski F editor. Hematology of Infancy and Childhood. Philadelphia: WB Saunders; 1993;p. 216
  7. Hall JG. Thrombocytopenia and absent radius (TAR) syndrome. J Med Genet. 1987;24:79–83
  8. Whitfields M, Barr DG. Cow's milk allergy in the syndrome of thrombocytopenia with absent radii. Arch Dis Child. 1976;51:337–343
  9. Skorka A, Bielicka-Cymermann J, Gieruszczak-Bialek D, Korniszewski L. Thrombocytopenia-absent radius (tar) syndrome: a case with agenesis of the corpus callosum, hypoplasia of cerebellar vermis and horseshoe kidney. Genet Couns. 2005;16:377–382
  10. Alter BP, D'Andrea AD. Inherited bone marrow failure syndromes. In:  Handin RI,  Lux SE,  Stossel TP editor. Blood: Principles and Practice of Hematology. 2nd ed.. Philadelphia: Lippincott Williams & Wilkins; 2003;p. 209–272
  11. Ballmaier M, Schulze H, Strauss G, et al. Thrombopoietin in patients with congenital thrombocytopenia and absent radii: elevated serum levels, normal receptor expression, but defective reactivity to thrombopoietin. Blood. 1997;90:612–619
  12. Sekine I, Hagiwara T, Miyazaki H, et al. Thrombocytopenia with absent radii syndrome: studies on serum thrombopoietin levels and megakaryopoiesis in vitro. J Pediatr Hematol Oncol. 1998;20:74–78
  13. al-Jefri AH, Dror Y, Bussel JB, Freedman MH. Thrombocytopenia with absent radii: frequency of marrow megakaryocyte progenitors, proliferative characteristics, and megakaryocyte growth and development factor responsiveness. Pediatr Hematol Oncol. 2000;17:299–306
  14. Letestu R, Vitrat N, Massé A, et al. Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome. Blood. 2000;95:1633–1641
  15. Homans AC, Cohen JL, Mazur EM. Defective megakaryocytopoiesis in the syndrome of thrombocytopenia with absent radii. Br J Haematol. 1988;70:205–210
  16. Bartley TD, Bogenberger J, Hunt P, et al. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor. Mpl. Cell. 1994;77:1117–1124
  17. Broudy VC, Kaushansky K. Biology of thrombopoietin. Curr Opin Pediatr. 1998;10:60–64
  18. Bonsi L, Grossi A, Strippoli P, et al. An erythroid and megakaryocytic common precursor cell line (B1647) expressing both c-mpl and erythropoietin receptor (Epo-R) proliferates and modifies globin chain synthesis in response to megakaryocyte growth and development factor (MGDF) but not to erythropoietin (Epo). Br J Haematol. 1997;98:549–559
  19. Brizzi MF, Battaglia E, Rosso A, et al. Regulation of polymorphonuclear cell activation by thrombopoietin. J Clin Invest. 1997;99:1576–1584
  20. Vigon I, Mornon JP, Cocault L, et al. Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily. PNAS. 1992;89:5640–5644
  21. Vigon I, Florindo C, Fichelson S, et al. Characterization of the murine MPL proto-oncogene, a member of the hemopoietic cytokine receptor family: molecular cloning, chromosomal location and evidence for a function in cell growth. Oncogene. 1993;8:2607–2615
  22. Ballmaier M, Schulze H, Cremer M, Folman CC, Strauss G, Welte K. Defective c-Mpl signaling in the syndrome of thrombocytopenia with absent radii. Stem Cells. 1998;16(Suppl 2):S177–S184
  23. Strauss G, Ballmaier M, Schulze H, Bogenberger J, Riehm H, Welte K. Significance of thrombopoietin and its receptor c-Mpl in regulation of thrombocytopoiesis in thrombocytopenia. Klin Padiatr. 1996;208:168–171
  24. De Alarcon PA, Graeve JA, Levine RF, McDonald TP, Beal DW. Thrombocytopenia and absent radii syndrome: defective megakaryocytopoiesis-thrombocytopoiesis. Am J Pediatr Hematol Oncol. 1991;13:77–83
  25. Strippoli P, Savoia A, Iolascon . A, et al. Mutational screening of thrombopoietin receptor gene (c-mpl) in patients with congenital thrombocytopenia and absent radii (TAR). Br J Haematol. 1998;103:311–314
  26. Fleischman RA, Letestu R, Mi X, et al. Absence of mutations in the HoxA10, HoxA11 and HoxD11 nucleotide coding sequences in thrombocytopenia with absent radius syndrome. Br J Haematol. 2002;116:367–375
  27. Christiansen J, Dyck JD, Elyas BG, et al. Chromosome 1q21.1 contiguous gene deletion is associated with congenital heart disease. Circ Res. 2004;94:1429–1435
  28. Klopocki E, Schulze H, Strauss G, et al. Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome. Am J Hum Genet. 2007;80:232–240
  29. Noma T, Glick AB, Geiser AG, et al. Molecular cloning and structure of the human transforming growth factor-beta 2 gene promoter. Growth Factors. 1991;4:247–255
  30. Pelton RW, Saxena B, Jones M, Moses HL, Gold LI. Immunohistochemical localization of TGF beta 1, TGF beta 2, TGF beta 3 in the mouse embryo: expression pattern suggests multiple roles during embryonic development. J Cell Biol. 1991;115:1091–1105
  31. Shull MM, Ormsby I, Kier AB, et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature. 1992;359:693–699
  32. Sanford PL, Ormsby I, Gittenberger-de Groot AC, et al. TGFb2 Knockout mice have multiple developmental defects that are non-overlapping with other TGFβ knockout phenotypes. Development. 1997;124:2659–2670
  33. Marchionni C, Tonelli R, Pierdomenico L, et al. Transforming growth factor b2 (TGFb2) gene structure and mutational screening in patients with congenital thrombocytopaenia with absent radii (TAR). Proceedings of the 32nd Annual Scientific Meeting of the International Society for Experimental Hematology, Paris, France, July 5–8, 2003.
  34. Marchionni C, Tonelli R, Pantucci E, et al. Mutational screening of transforming growth factor beta 2 (TGF-beta 2) gene in patients with congenital thrombocytopaenia with absent radii (TAR). Proceedings of the VI Convegno Nazionale I.N.B.B. Napoli, November 4–6, 2004.
  35. Pierdomenico L, Bonsi L, Calvitti M, et al. Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp. Transplantation. 2005;80:836–842
  36. Alviano F, Fossati V, Marchionni C, et al. Term Amniotic membrane is a high throughput source for multipotent Mesenchymal Stem Cells with the ability to differentiate into endothelial cells in vitro. BMC Dev Biol. 2007;7:11
  37. Sanz-Rodriguez F, Guerrero-Esteo M, Botella LM, Banville D, Vary CP, Bernabéu C. Endoglin regulates cytoskeletal organization through binding to ZRP-1, a member of the Lim family of proteins. J Biol Chem. 2004;279:32858–32868
  38. Llorca O, Trujillo A, Blanco FJ, Bernabeu C. Structural model of human endoglin, a transmembrane receptor responsible for hereditary hemorrhagic telangiectasia. J Mol Biol. 2007;365:694–705
  39. Michalevicz R, Baron S, Burstein Y. Osteoclast-like cells grow in cultures of multipotent hematopoietic progenitors in thrombocytopenia and absent radii (TAR) syndrome. Isr J Med Sci. 1988;24:42–45
  40. Dominici M, Pritchard C, Garlits JE, Hofmann TJ, Persons DA, Horwitz EM. Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation. Proc Natl Acad Sci U S A. 2004;101:11761-1176
  41. Bussel JB, Kuter DJ, George JN, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006;19(355):1672–1681
  42. Kantarjian H, Fenaux P, Sekeres MA, et al. Phase 1/2 Study of AMG 531 in thrombocytopenic patients (PTS) with low-risk myelodysplastic syndrome (MDS): Update including extended treatment. Blood (ASH Annual Meeting Abstracts). 2007;110:250
  43. Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;29(357):2237–2247

PII: S0301-472X(08)00421-9

doi: 10.1016/j.exphem.2008.09.004

Experimental Hematology
Volume 37, Issue 1 , Pages 1-7 , January 2009

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