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Blood, 1 January 2007, Vol. 109, No. 1, pp. 93-99. Prepublished online as a Blood First Edition Paper on September 19, 2006; DOI 10.1182/blood-2006-02-004275. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2006-02-004275v1 109/1/93    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Germeshausen, M. Articles by Welte, K. Search for Related Content PubMed PubMed Citation Articles by Germeshausen, M. Articles by Welte, K. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 17, 2006 Accepted August 9, 2006 Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis - results of a long-term survey Manuela Germeshausen*, Matthias Ballmaier, and Karl Welte Deptartment of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany * Corresponding author; email: germeshausen.manuela{at}mh-hannover.de. Point mutations in the gene for the G-CSF receptor CSF3R have been implicated in the progression of severe congenital neutropenia (CN) to leukemia. In this study we present data on a total of 218 patients with chronic neutropenia, including 148 patients with CN (23/148 with secondary malignancies). We detected CSF3R nonsense mutations at 17 different nucleotide positions (thereof 10 new mutations) which lead to a loss of one to all 4 tyrosine residues in the intracellular domain of the receptor. 18 out of 23 CN (78%) patients with signs of malignant transformation were shown to harbor a CSF3R mutation, indicating that these mutations, although not a necessary condition, are highly predictive for malignant transformation even if detected in a low percentage of transcripts. In serial analyses of 50 patients with CSF3R mutations we were able to follow the clonal dynamics of mutated cells. We could demonstrate that even a highly clonal hematopoiesis did not inevitably show a rapid progression to leukemia. Our results strongly suggest that acquisition of a CSF3R mutation is an early event in leukemogenesis which has to be accompanied by cooperating molecular events which remain to be defined. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Drifting precariously due to lost tyrosines Peter D. Emanuel Blood 2007 109: 7-8. [Full Text] [PDF] This article has been cited by other articles: M. Germeshausen, C. P. Kratz, M. Ballmaier, and K. Welte RAS and CSF3R mutations in severe congenital neutropenia Blood, October 15, 2009; 114(16): 3504 - 3505. [Full Text] [PDF] K. Beel and P. Vandenberghe G-CSF receptor (CSF3R) mutations in X-linked neutropenia evolving to acute myeloid leukemia or myelodysplasia Haematologica, October 1, 2009; 94(10): 1449 - 1452. [Abstract] [Full Text] [PDF] I. Plo, Y. Zhang, J.-P. Le Couedic, M. Nakatake, J.-M. Boulet, M. Itaya, S. O. Smith, N. Debili, S. N. Constantinescu, W. Vainchenker, et al. An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia J. Exp. Med., August 3, 2009; 206(8): 1701 - 1707. [Abstract] [Full Text] [PDF] M. Germeshausen, K. Welte, and M. Ballmaier In vivo expansion of cells expressing acquired CSF3R mutations in patients with severe congenital neutropenia Blood, January 15, 2009; 113(3): 668 - 670. [Abstract] [Full Text] [PDF] M. Germeshausen, M. Grudzien, C. Zeidler, H. Abdollahpour, S. Yetgin, N. Rezaei, M. Ballmaier, B. Grimbacher, K. Welte, and C. Klein Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations Blood, May 15, 2008; 111(10): 4954 - 4957. [Abstract] [Full Text] [PDF] L. Hennighausen and G. W. Robinson Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B Genes & Dev., March 15, 2008; 22(6): 711 - 721. [Abstract] [Full Text] [PDF] D. C. Link, G. Kunter, Y. Kasai, Y. Zhao, T. Miner, M. D. McLellan, R. E. Ries, D. Kapur, R. Nagarajan, D. C. Dale, et al. Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia Blood, September 1, 2007; 110(5): 1648 - 1655. [Abstract] [Full Text] [PDF] E. G. Blanchard and S. J. Corey Filgrastim therapy: a bone of contention Blood, April 15, 2007; 109(8): 3125 - 3126. [Full Text] [PDF] I. P. Touw and M. Bontenbal Granulocyte Colony-Stimulating Factor: Key (F)actor or Innocent Bystander in the Development of Secondary Myeloid Malignancy? J Natl Cancer Inst, February 7, 2007; 99(3): 183 - 186. [Full Text] [PDF]

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