PMID- 14687986
OWN - NLM
STAT- MEDLINE
DCOM- 20060406
LR  - 20111117
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Linking)
VI  - 88
IP  - 12
DP  - 2003 Dec
TI  - Lhx2 expression in hematopoietic progenitor/stem cells in vivo causes a chronic 
      myeloproliferative disorder and altered globin expression.
PG  - 1336-47
AB  - BACKGROUND AND OBJECTIVES: Chronic myeloproliferative disorders (CMDs) are 
      thought to be due to mutation(s) in a single clone at the level of the 
      hematopoietic stem cell (HSC). Such mutations and additional mutations causing 
      progression of the disease are largely unknown. Chronic myeloid leukemia (CML) is 
      a CMD characterized by a chromosomal translocation between chromosomes 9 and 22 
      creating the fusion protein BCR-ABL. This translocation has also been suggested 
      to cause mis-expression of the LIM-homeobox gene Lhx2 in hematopoietic cells. We 
      have previously shown that Lhx2 expression in mouse HSC generates 
      cytokine-dependent stem cell-like cell lines that can produce long-term 
      repopulation in stem cell-deficient mice. DESIGN AND METHODS: Since the 
      consequences of Lhx2 expression in hematopoietic cells in vivo were unknown, mice 
      engrafted with the stem cell-like cell lines were analyzed in detail for any 
      pathologic changes. RESULTS: Expression of Lhx2 was maintained in vivo and most 
      engrafted mice developed a myeloproliferative disorder characterized by 
      splenomegaly, extramedullary hematopoiesis and anemia. The disorder was 
      transplantable and the Lhx2-expressing cells could also cause acute leukemia. The 
      anemia was due to both a reduced number of circulating erythrocytes and a reduced 
      mean corpuscular hemoglobin concentration (MCHC). INTERPRETATION AND CONCLUSIONS: 
      These observations suggest that constitutive expression of Lhx2 in hematopoietic 
      cells causes CMD, and also that a novel cell-autonomous mechanism can contribute 
      to anemia.
FAU - Richter, Karin
AU  - Richter K
AD  - Umea Center for Molecular Medicine, Umea University, 901 87 Umea, Sweden.
FAU - Pinto do O, Perpetua
AU  - Pinto do O P
FAU - Hagglund, Anna-Carin
AU  - Hagglund AC
FAU - Wahlin, Anders
AU  - Wahlin A
FAU - Carlsson, Leif
AU  - Carlsson L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Homeodomain Proteins)
RN  - 0 (LIM-Homeodomain Proteins)
RN  - 0 (Lhx2 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 9004-22-2 (Globins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 5.3.1.9 (Glucose-6-Phosphate Isomerase)
SB  - IM
MH  - Anemia/genetics
MH  - Animals
MH  - Bone Marrow/pathology
MH  - Chronic Disease
MH  - Colony-Forming Units Assay
MH  - Disease Progression
MH  - Erythrocyte Count
MH  - Erythrocyte Indices
MH  - Gene Expression Regulation, Leukemic
MH  - Globins/*biosynthesis/genetics
MH  - Glucose-6-Phosphate Isomerase/genetics
MH  - Hematopoiesis, Extramedullary/genetics
MH  - Hematopoietic Stem Cell Transplantation/adverse effects
MH  - Hematopoietic Stem Cells/*pathology
MH  - Homeodomain Proteins/genetics/*physiology
MH  - LIM-Homeodomain Proteins
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/pathology
MH  - Leukemia, Myeloid/genetics/pathology
MH  - Leukocyte Count
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Cells/pathology
MH  - Myeloproliferative Disorders/*genetics/pathology
MH  - Proto-Oncogene Proteins c-kit/genetics
MH  - Proviruses/genetics
MH  - Radiation Chimera
MH  - Spleen/pathology
MH  - Splenomegaly/etiology
MH  - Transcription Factors/genetics/*physiology
MH  - Transduction, Genetic
EDAT- 2003/12/23 05:00
MHDA- 2006/04/07 09:00
CRDT- 2003/12/23 05:00
PHST- 2003/12/23 05:00 [pubmed]
PHST- 2006/04/07 09:00 [medline]
PHST- 2003/12/23 05:00 [entrez]
PST - ppublish
SO  - Haematologica. 2003 Dec;88(12):1336-47.