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Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2002-03-0852.
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Blood, 15 October 2002, Vol. 100, No. 8, pp. 2980-2988
NEOPLASIA
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
From the Departments of Hematology and Oncology,
Virology, and Immunology, Istituto Superiore di Sanità, Rome;
Department of Cellular Biotechnology and Hematology, University "La
Sapienza," Rome, Italy; and Kimmel Cancer Center, Thomas Jefferson
University, Philadelphia, PA.
We have investigated the expression of interleukin-3 receptor  (IL-3R) 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-3R 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-3R
expression was associated with peculiar properties of leukemic blasts,
specifically in 3 areas. First, in all patients the blasts expressing
elevated IL-3R 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-3R expression. Third, following IL-3 treatment,
Stat5 was activated at higher levels in blasts with elevated IL-3R
expression. At the clinical level, a significant correlation was
observed between the level of IL-3R expression and the number of
leukemic blasts at diagnosis, and patients exhibiting elevated IL-3R
levels had a lower complete remission rate and survival duration than
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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