PMID- 10498627
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20190508
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 7
DP  - 1999 Oct 1
TI  - Erythropoietin receptor mutations associated with familial erythrocytosis cause
      hypersensitivity to erythropoietin in the heterozygous state.
PG  - 2530-2
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.
FAU - Watowich, S S
AU  - Watowich SS
AD  - Department of Immunology, MD Anderson Cancer Center, Houston, TX, USA.
FAU - Xie, X
AU  - Xie X
FAU - Klingmuller, U
AU  - Klingmuller U
FAU - Kere, J
AU  - Kere J
FAU - Lindlof, M
AU  - Lindlof M
FAU - Berglund, S
AU  - Berglund S
FAU - de la Chapelle, A
AU  - de la Chapelle A
LA  - eng
GR  - CA-16058/CA/NCI NIH HHS/United States
GR  - CA-77447/CA/NCI NIH HHS/United States
GR  - R01 CA077447-03/CA/NCI NIH HHS/United States
GR  - CA-67941/CA/NCI NIH HHS/United States
GR  - R01 CA077447-02/CA/NCI NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Milk Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Erythropoietin)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 11096-26-7 (Erythropoietin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - AIM
SB  - IM
MH  - DNA-Binding Proteins/blood
MH  - Erythrocyte Count
MH  - Erythroid Precursor Cells/*drug effects/pathology/physiology
MH  - Erythropoietin/*blood/*pharmacology
MH  - Female
MH  - Genes, Dominant
MH  - Heterozygote
MH  - Humans
MH  - Janus Kinase 2
MH  - Leukocyte Count
MH  - Male
MH  - *Milk Proteins
MH  - Mutation
MH  - Pedigree
MH  - Platelet Count
MH  - Polycythemia/blood/*genetics
MH  - Protein-Tyrosine Kinases/blood
MH  - *Proto-Oncogene Proteins
MH  - Receptors, Erythropoietin/*genetics
MH  - STAT5 Transcription Factor
MH  - Trans-Activators/blood
EDAT- 1999/09/25 00:00
MHDA- 1999/09/25 00:01
CRDT- 1999/09/25 00:00
PHST- 1999/09/25 00:00 [pubmed]
PHST- 1999/09/25 00:01 [medline]
PHST- 1999/09/25 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Oct 1;94(7):2530-2.