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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3530-3537. Prepublished online as a Blood First Edition Paper on August 1, 2006; DOI 10.1182/blood-2006-04-013813. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-013813v1 108/10/3530    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yalcintepe, L. Articles by Hogge, D. E. Search for Related Content PubMed PubMed Citation Articles by Yalcintepe, L. Articles by Hogge, D. E. Related Collections Stem Cells in Hematology Hematopoiesis and Stem Cells Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Expression of interleukin-3 receptor subunits on defined subpopulations of acute myeloid leukemia blasts predicts the cytotoxicity of diphtheria toxin interleukin-3 fusion protein against malignant progenitors that engraft in immunodeficient mice Leman Yalcintepe, Arthur E. Frankel, and Donna E. Hogge From the Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; and the Scott and White Memorial Hospital, Temple, TX. The interleukin-3 receptor (IL-3R) subunits are overexpressed on acute myeloid leukemia (AML) blasts compared with normal hematopoietic cells and are thus potential targets for novel therapeutic agents. Both fluorescence-activated cell sorter (FACS) analysis and quantitative real-time reverse transcription-polymerase chain reaction (QRT-PCR) were used to quantify expression of the IL-3R and c subunits on AML cells. QRT-PCR for both subunits was most predictive of killing of AML colony-forming cells (AML-CFCs) by diphtheria toxin-IL-3 fusion protein (DT388IL3). Among 19 patient samples, the relative level of the IL-3R was higher than the IL-3Rc and highest in CD34+CD38-CD71- cells, enriched for candidate leukemia stem cells, compared with cell fractions depleted of such progenitors. Overall, the amount of IL-3Rc subunit did not vary among sorted subpopulations. However, expression of both subunits varied by more than 10-fold among different AML samples for all subpopulations studied. The level of IL-3Rc expression versus glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (set at 1000) ranged from 0.14 to 13.56 in CD34+CD38-CD71- cells from different samples; this value was correlated (r = .76, P = .05) with the ability of DT388IL3 to kill AML progenitors that engraft in 2-microglobin-deficient nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice (n = 7). Thus, quantification of IL-3R subunit expression on AML blasts predicts the effectiveness IL-3R-targeted therapy in killing primitive leukemic progenitors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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