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Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2002-03-0852. This Article Full Text (PDF) All Versions of this Article: 2002-03-0852v1 100/8/2980    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 Testa, U. Articles by Peschle, C. Search for Related Content PubMed PubMed Citation Articles by Testa, U. Articles by Peschle, C. Social Bookmarking                   What's this? Submitted March 19, 2002 Accepted June 5, 2002 Elevated expression of IL-3R in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis Ugo Testa*, Roberta Riccioni, Stefania Militi, Eliana Coccia, Emilia Stellacci, Paola Samoggia, Roberto Latagliata, Gualtiero Mariani, Annalisa Rossini, Angela Battistini, Francesco Lo-Coco, and Cesare Peschle Department of Hematology and Oncology, Istituto Superiore di Sanita, Rome, Italy Department of Virology, Istituto Superiore di Sanita, Rome, Italy Department of Immunology, Istituto Superiore di Sanita, Rome, Italy Cellular Biotechnology and Hematology, University 'La Sapienza', Rome, Italy Department of Hematology and Oncology, Istituto Superiore di Sanita, Rome, Italy; Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA * Corresponding author; email: u.testa{at}iss.it. We have investigated the expression of interleukin-3 receptor (IL-3R) chain in primary blasts from 79 acute myeloid leukemia (AML), 25 B acute lymphoid leukemia (B-ALL) and 7 T acute lymphoid leukemia (T-ALL) patients to evaluate a linkage between the expression of this receptor chain, blast proliferative status and disease prognosis. While in the majority of T-ALL IL-3R chain was scarcely expressed, it was overexpressed in 40 and 45% of B-ALL and AML cases, respectively, as compared to the levels observed in normal CD34+ progenitors. The biological and clinical significance of this overexpression pattern was investigated in AMLs. At biological level, the elevated IL-3R expression was associated with peculiar properties of leukemic blasts. Specifically, (i) in all cases the blasts expressing an elevated IL-3R level exhibited both higher cycling activity and increased resistance to apoptosis triggered by growth factor deprivation; (ii) Spontaneous Stat5 phosphorylation was observed in 13% of AML patients, all pertaining to the group of patients exhibiting high IL-3R expression; (iii) following IL-3 treatment, Stat5 was activated at higher level in blasts with elevated IL-3R expression. At the clinical level, (i) a significant correlation was observed between the level of IL-3R expression and the number of leukemic blasts at diagnosis; (ii) patients exhibiting elevated IL-3R levels had a lower complete remission rate and survival duration, as compared to those showing normal IL-3R levels. These findings suggest that in AML deregulated expression of IL-3R may contribute to the proliferative advantage of the leukemic blasts and hence to a poor prognosis. 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