Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis.
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.
D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000032:analysis; D017209:Apoptosis; D001752:Blast Crisis; D002453:Cell Cycle; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053650:Interleukin-3 Receptor alpha Subunit; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016185:Receptors, Interleukin-3 / Q000235:genetics*; D012008:Recurrence; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D016185:Receptors, Interleukin-3