TY - JOUR
T1 - Erythropoietin receptor mutations associated with familial erythrocytosis cause hypersensitivity to erythropoietin in the heterozygous state
AU - Watowich, Stephanie S.
AU - Xie, Xiaoling
AU - Klingmuller, Ursula
AU - Kere, Juha
AU - Lindlof, Mikael
AU - Berglund, Stig
AU - De La Chapelle, Albert
PY - 1999/10/1
Y1 - 1999/10/1
N2 - Inherited mutations in the erythropoietin receptor (EPOR) causing premature termination of the receptor cytoplasmic region are associated with dominant familial erythrocytosis (FE), a benign clinical condition characterized by hypersensitivity of erythroid progenitor cells to EPO and low serum EPO (S-EPO) levels. We describe a Swedish family with dominant FE in which erythrocytosis segregates with a new truncation in the negative control domain of the EPOR. We show that cells engineered to concomitantly express the wild-type (WT) EPOR and mutant EPORs associated with FE (FE EPORs) are hypersensitive to EPO-stimulated proliferation and activation of Jak2 and Stat5. These results demonstrate that FE is caused by hyperresponsiveness of receptor-mediated signaling pathways and that this is dominant with respect to WT EPOR signaling.
AB - Inherited mutations in the erythropoietin receptor (EPOR) causing premature termination of the receptor cytoplasmic region are associated with dominant familial erythrocytosis (FE), a benign clinical condition characterized by hypersensitivity of erythroid progenitor cells to EPO and low serum EPO (S-EPO) levels. We describe a Swedish family with dominant FE in which erythrocytosis segregates with a new truncation in the negative control domain of the EPOR. We show that cells engineered to concomitantly express the wild-type (WT) EPOR and mutant EPORs associated with FE (FE EPORs) are hypersensitive to EPO-stimulated proliferation and activation of Jak2 and Stat5. These results demonstrate that FE is caused by hyperresponsiveness of receptor-mediated signaling pathways and that this is dominant with respect to WT EPOR signaling.
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U2 - 10.1182/blood.v94.7.2530.419k35_2530_2532
DO - 10.1182/blood.v94.7.2530.419k35_2530_2532
M3 - Article
C2 - 10498627
AN - SCOPUS:0033215521
SN - 0006-4971
VL - 94
SP - 2530
EP - 2532
JO - Blood
JF - Blood
IS - 7
ER -