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Elevated expression of IL-3Rα in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis

Testa, Ugo, Riccioni, Roberta, Militi, Stefania, Coccia, Eliana, Stellacci, Emilia, Samoggia, Paola, Latagliata, Roberto, Mariani, Gualtiero, Rossini, Annalisa, Battistini, Angela, Lo-Coco, Francesco, Peschle, Cesare·2002·Blood

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.

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Cited by

Metadata

Authors
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.
Venue
Blood
Published
2002-10-15
Volume
100
Issue
8
Pages
2980-2988
ISSN
  • 1528-0020
  • 0006-4971
Cited by
296
References
1
Language
en

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