A Truncated Isoform of the Human β Chain Common to the Receptors for Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin-3 (IL-3), and IL-5 With Increased mRNA Expression in Some Patients With Acute Leukemia

Abstract

AbstractWe report here a naturally occurring isoform of the human β chain common to the receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 (GMRβC) with a truncated intracytoplasmic tail caused by deletion of a 104-bp exon in the membrane-proximal region of the chain. This β intracytoplasmic truncated chain (βIT) has a predicted tail of 46 amino acids, instead of 432 for βC, with 23 amino acids in common with βC and then a new sequence of 23 amino acids. In primary myeloid cells, βIT comprised approximately 20% of the total β chain message, but was increased up to 90% of total in blast cells from a significant proportion of patients with acute leukemia. Specific anti-βITantibodies demonstrated its presence in primary myeloid cells and cell lines. Coexpression of βIT converted low-affinity GMRα chains (KD 2.5 nmol/L) to higher-affinity αβ complexes (KD 200 pmol/L). These could bind JAK2 that was tyrosine-phosphorylated by stimulation with GM-CSF. βITdid not support GM-CSF–induced proliferation when cotransfected with GMRα into CTLL-2 cells. Therefore, it may interfere with the signal-transducing properties of the βC chain and play a role in the pathogenesis of leukemia.