Elevated expression of IL-3Rα 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, Cesare Peschle

Research output: Contribution to journalArticle

Abstract

We have investigated the expression of interleukin-3 receptor α (IL-3Rα) chain in primary blasts from 79 patients with acute myeloid leukemia (AML), 25 patients with B-acute lymphoid leukemia (B-ALL), and 7 patients with T-acute lymphoid leukemia (T-ALL) to evaluate a linkage between the expression of this receptor chain, blast proliferative status, and disease prognosis. Although IL-3Rα chain was scarcely expressed in most patients with T-ALL, it was overexpressed in 40% and 45% of patients with B-ALL and AML, respectively, compared with the levels observed in normal CD34 + progenitors. The biological and clinical significance of this overexpression pattern was investigated in AML. At the biological level, elevated IL-3Rα expression was associated with peculiar properties of leukemic blasts, specifically in 3 areas. First, in all patients the blasts expressing elevated IL-3Rα levels exhibited higher cycling activity and increased resistance to apoptosis triggered by growth factor deprivation. Second, spontaneous signal transducer and activator of transcription 5 (Stat5) phosphorylation was observed in 13% of AML patients, all pertaining to the group of patients exhibiting high IL-3Rα expression. Third, following IL-3 treatment, Stat5 was activated at higher levels in blasts with elevated IL-3Rα expression. At the clinical level, a significant correlation was observed between the level of IL-3Rα expression and the number of leukemic blasts at diagnosis, and patients exhibiting elevated IL-3Rα levels had a lower complete remission rate and survival duration than those showing normal IL-3Rα levels. These findings suggest that in AML, deregulated expression of IL-3Rα may contribute to the proliferative advantage of the leukemic blasts and, hence, to a poor prognosis.

Original languageEnglish
Pages (from-to)2980-2988
Number of pages9
JournalBlood
Volume100
Issue number8
DOIs
Publication statusPublished - Oct 15 2002

ASJC Scopus subject areas

  • Hematology

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    Testa, U., Riccioni, R., Militi, S., Coccia, E., Stellacci, E., Samoggia, P., Latagliata, R., Mariani, G., Rossini, A., Battistini, A., Lo-Coco, F., & Peschle, C. (2002). Elevated expression of IL-3Rα in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis. Blood, 100(8), 2980-2988. https://doi.org/10.1182/blood-2002-03-0852