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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2764-2769. Prepublished online as a Blood First Edition Paper on June 29, 2006; DOI 10.1182/blood-2006-04-012260. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-012260v1 108/8/2764    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Pollard, J. A. Articles by Meshinchi, S. Search for Related Content PubMed PubMed Citation Articles by Pollard, J. A. Articles by Meshinchi, S. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA FLT3 internal tandem duplication in CD34+/CD33- precursors predicts poor outcome in acute myeloid leukemia Jessica A. Pollard, Todd A. Alonzo, Robert B. Gerbing, William G. Woods, Beverly J. Lange, David A. Sweetser, Jerald P. Radich, Irwin D. Bernstein, and Soheil Meshinchi From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; the Department of Pediatrics, University of Washington Medical Center, Seattle; the Department of Biostatistics, University of Southern California Keck School of Medicine, Los Angeles; the Children's Oncology Group, Arcadia, CA; the Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, GA; the Department of Oncology, Children's Hospital of Philadelphia, PA; and the Department of Pediatric Hematology/Oncology, Mass General Hospital for Children, Boston, MA. Acute myeloid leukemia (AML) is a clonal disease characterized by heterogeneous involvement of hematopoietic stem cell/progenitor cell populations. Using FLT3 internal tandem duplication (FLT3/ITD) as a molecular marker, we tested the hypothesis that clinical outcome in AML correlates with disease involvement of CD34+/CD33- precursors. Diagnostic specimens from 24 children with FLT3/ITD-positive AML were sorted by fluorescence-activated cell sorting (FACS), and resultant CD34+/CD33- and CD34+/CD33+ progenitors were analyzed directly and after colony-forming cell (CFC) assay for the presence of FLT3/ITD. FLT3/ITD was present in all CD34+/CD33+ patient samples. In contrast, FLT3/ITD was detected in CD34+/CD33- progenitors in only 19 of 24 samples. A bipotent progenitor was affected in a subset of patients, as evidenced by the presence of FLT3/ITD in both granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) colonies. Those patients in whom CD34+/CD33- precursors harbored the FLT3/ITD had worse clinical outcome; actuarial event-free survival (EFS) at 4 years from study entry for those patients with and without FLT3/ITD detection in CD34+/CD33- progenitors was 11% ± 14% versus 100% ± 0%, respectively (P = .002). This study suggests that FLT3/ITD involvement in CD34+/CD33- precursors is heterogeneous and that detection of the mutation in the less-mature progenitor population may be associated with disease resistance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: FLT3: the root of the problem Mark Levis Blood 2006 108: 2501-2502. [Full Text] [PDF] This article has been cited by other articles: S. Vempati, C. Reindl, U. Wolf, R. Kern, K. Petropoulos, V. M. Naidu, C. Buske, W. Hiddemann, T. M. Kohl, and K. Spiekermann Transformation by Oncogenic Mutants and Ligand-Dependent Activation of FLT3 Wild-type Requires the Tyrosine Residues 589 and 591 Clin. Cancer Res., July 15, 2008; 14(14): 4437 - 4445. [Abstract] [Full Text] [PDF] L. Li, O. Piloto, H. B. Nguyen, K. Greenberg, K. Takamiya, F. Racke, D. Huso, and D. Small Knock-in of an internal tandem duplication mutation into murine FLT3 confers myeloproliferative disease in a mouse model Blood, April 1, 2008; 111(7): 3849 - 3858. [Abstract] [Full Text] [PDF] S. Vempati, C. Reindl, S. K. Kaza, R. Kern, T. Malamoussi, M. Dugas, G. Mellert, S. Schnittger, W. Hiddemann, and K. Spiekermann Arginine 595 is duplicated in patients with acute leukemias carrying internal tandem duplications of FLT3 and modulates its transforming potential Blood, July 15, 2007; 110(2): 686 - 694. [Abstract] [Full Text] [PDF]

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