We have investigated the expression of interleukin-3 receptor alpha (IL-3Ralpha) 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-3Ralpha 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-3Ralpha expression was associated with peculiar properties of leukemic blasts, specifically in 3 areas. First, in all patients the blasts expressing elevated IL-3Ralpha 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-3Ralpha expression. Third, following IL-3 treatment, Stat5 was activated at higher levels in blasts with elevated IL-3Ralpha expression. At the clinical level, a significant correlation was observed between the level of IL-3Ralpha expression and the number of leukemic blasts at diagnosis, and patients exhibiting elevated IL-3Ralpha levels had a lower complete remission rate and survival duration than those showing normal IL-3Ralpha levels. These findings suggest that in AML, deregulated expression of IL-3Ralpha may contribute to the proliferative advantage of the leukemic blasts and, hence, to a poor prognosis.

Testa, U., Riccioni, R., Militi, S., Coccia, E., Stellacci, E., Samoggia, P., et al. (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 [10.1182/blood-2002-03-0852].

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

LO COCO, FRANCESCO;
2002

Abstract

We have investigated the expression of interleukin-3 receptor alpha (IL-3Ralpha) 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-3Ralpha 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-3Ralpha expression was associated with peculiar properties of leukemic blasts, specifically in 3 areas. First, in all patients the blasts expressing elevated IL-3Ralpha 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-3Ralpha expression. Third, following IL-3 treatment, Stat5 was activated at higher levels in blasts with elevated IL-3Ralpha expression. At the clinical level, a significant correlation was observed between the level of IL-3Ralpha expression and the number of leukemic blasts at diagnosis, and patients exhibiting elevated IL-3Ralpha levels had a lower complete remission rate and survival duration than those showing normal IL-3Ralpha levels. These findings suggest that in AML, deregulated expression of IL-3Ralpha may contribute to the proliferative advantage of the leukemic blasts and, hence, to a poor prognosis.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - Malattie del Sangue
English
Adult; Aged; Antigens, Surface; Apoptosis; Blast Crisis; Cell Cycle; Gene Expression Regulation, Neoplastic; Humans; Interleukin-3 Receptor alpha Subunit; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Middle Aged; Predictive Value of Tests; Prognosis; Receptors, Interleukin-3; Recurrence; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Survival Rate; Tumor Cells, Cultured
Testa, U., Riccioni, R., Militi, S., Coccia, E., Stellacci, E., Samoggia, P., et al. (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 [10.1182/blood-2002-03-0852].
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
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/162065
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