PMID- 10557054
OWN - NLM
STAT- MEDLINE
DCOM- 19991207
LR  - 20190915
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 13
IP  - 11
DP  - 1999 Nov
TI  - The Tel-PDGFRbeta fusion gene produces a chronic myeloproliferative syndrome in
      transgenic mice.
PG  - 1790-803
AB  - Chronic myelomonocytic leukemia (CMML) is a pre-leukemic syndrome that displays
      both myelodysplastic and myeloproliferative features. The t(5;12) chromosomal
      translocation, present in a subset of CMML patients with myeloproliferation fuses
      the amino terminal portion of the ets family member, Tel, with the transmembrane 
      and tyrosine kinase domains of platelet-derived growth factor receptor beta
      (PDGFRbeta) gene. To investigate the role of this fusion protein in the
      pathogenesis of CMML, we expressed the Tel-PDGFRbeta fusion cDNA in hematopoietic
      cells of transgenic mice under the control of the human CD11a promoter.
      Transgenic founders and their offspring express the transgene specifically in
      hematopoietic tissues and develop a myeloproliferative syndrome characterized by:
      overproduction of mature neutrophils and megakaryocytes in the bone marrow;
      splenomegaly with effacement of splenic architecture by extramedullary
      hematopoiesis; an abnormal population of leukocytes co-expressing lymphoid and
      myeloid markers; and increased numbers of colonies in in vitro bone marrow CFU
      assays. All mice expressing the transgene exhibited at least one of these
      features of dysregulated myelopoiesis, and 20% progressed to a myeloid or
      lymphoid malignancy. This murine model of CMML parallels a myeloproliferative
      syndrome in humans and implicates the Tel-PDGFRbeta fusion protein in its
      pathogenesis.
FAU - Ritchie, K A
AU  - Ritchie KA
AD  - Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108,
      USA.
FAU - Aprikyan, A A
AU  - Aprikyan AA
FAU - Bowen-Pope, D F
AU  - Bowen-Pope DF
FAU - Norby-Slycord, C J
AU  - Norby-Slycord CJ
FAU - Conyers, S
AU  - Conyers S
FAU - Bartelmez, S
AU  - Bartelmez S
FAU - Sitnicka, E H
AU  - Sitnicka EH
FAU - Hickstein, D D
AU  - Hickstein DD
LA  - eng
GR  - DK48708-02/DK/NIDDK NIH HHS/United States
GR  - K08HL02959/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ETS translocation variant 6 protein)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Bone Marrow/metabolism/pathology
MH  - Colony-Forming Units Assay
MH  - DNA-Binding Proteins/*genetics/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Hematopoiesis
MH  - Hematopoietic Stem Cells/metabolism/pathology
MH  - Leukemia, Myelomonocytic, Chronic/*genetics/pathology/physiopathology
MH  - Leukocytes/metabolism/pathology
MH  - Male
MH  - Megakaryocytes/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myeloproliferative Disorders/*genetics/pathology/physiopathology
MH  - Oncogene Proteins, Fusion/*genetics/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins c-ets
MH  - Receptor, Platelet-Derived Growth Factor beta/*genetics/metabolism
MH  - *Repressor Proteins
MH  - Spleen/metabolism/pathology
MH  - Transcription Factors/*genetics/metabolism
MH  - Transgenes/genetics
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
AID - 10.1038/sj.leu.2401494 [doi]
PST - ppublish
SO  - Leukemia. 1999 Nov;13(11):1790-803. doi: 10.1038/sj.leu.2401494.