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A Truncated Isoform of the Human  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
Rosemary E. Gale,
Robin W. Freeburn,
Asim Khwaja,
Rajesh Chopra, and
David C. Linch
From the Department of Haematology, University College London Medical
School, London, UK.
We report here a naturally occurring isoform of the human  chain
common to the receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 (GMRC)
with a truncated intracytoplasmic tail caused by deletion of a 104-bp exon in the membrane-proximal region of the chain. This intracytoplasmic truncated chain (IT) has a predicted
tail of 46 amino acids, instead of 432 for C, with 23 amino acids in common with C and then a new sequence of
23 amino acids. In primary myeloid cells, IT comprised
approximately 20% of the total chain message, but was increased up
to 90% of total in blast cells from a significant proportion of
patients with acute leukemia. Specific anti-IT antibodies demonstrated its presence in primary myeloid cells and cell
lines. Coexpression of IT converted low-affinity GMR chains (KD 2.5 nmol/L) to higher-affinity complexes
(KD 200 pmol/L). These could bind JAK2 that was
tyrosine-phosphorylated by stimulation with GM-CSF. IT
did not support GM-CSF-induced proliferation when cotransfected with
GMR into CTLL-2 cells. Therefore, it may interfere with the
signal-transducing properties of the C chain and play a
role in the pathogenesis of leukemia.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 54-63
© 1998 by The American Society of Hematology.
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