1: Leuk Res. 2005 Oct 7; [Epub ahead of print] 

Histologic and molecular characterizations of megakaryocytic leukemia in mice.

Hao X, Shin MS, Zhou JX, Lee CH, Qi CF, Naghashfar Z, Hartley JW, Fredrickson
TN, Ward JM, Morse HC 3rd.

Laboratory of Immunopathology, National Institute of Allergy and Infectious
Diseases, National Institute of Health, Rockville, MD 20852, USA.

Six cases of megakaryocytic leukemia (MKL) were identified and analyzed for
morphology and molecular features. MKL were composed of megakaryocyte lineage
cells ranging from immature to quite mature cells. VWF, GATA1 and RUNX1 were
strongly expressed in megakaryocytes in both normal spleen and MKL as analyzed
by immunohistochemistry (IHC). Altered expression of Meis1, Pbx1 and Psen2 and
Lef1 in MKL detected with oligonucleotide microarrays was confirmed by qPCR and
IHC. This is the first report of spontaneous MKL in mice, defining VWF as a
biomarker for diagnosis and suggesting possible involvement of a series of genes
in disease pathogenesis.

PMID: 16219351 [PubMed - as supplied by publisher]


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2: Dev Biol. 2005 Apr 15;280(2):307-20. 

The homeodomain protein Meis1 is essential for definitive hematopoiesis and
vascular patterning in the mouse embryo.

Azcoitia V, Aracil M, Martinez-A C, Torres M.

Departamento de Inmunologia y Oncologia, Centro Nacional de Biotecnologia/CSIC
UAM, Campus de Cantoblanco, Madrid, Spain.

Homeodomain proteins of the Meis subfamily are expressed dynamically in several
organs during embryogenesis and exert potent regulatory activity through their
interaction with Hox proteins and other transcription factors. Here we show that
Meis1 is expressed in the hematopoietic stem cell (HSC) compartment in the fetal
liver, and in the primary sites of definitive hematopoiesis, including the
aorta-gonad-mesonephros (AGM) mesenchyme, the hemogenic embryonic arterial
endothelium, and hematopoietic clusters within the aorta, vitelline, and
umbilical arteries. We inactivated the Meis1 gene in mice and found that Meis1
mutant mice die between embryonic days 11.5 and 14.5, showing internal
hemorrhage, liver hypoplasia, and anemia. In Meis1 mutant mouse fetal liver and
AGM, HSC compartments are severely underdeveloped and colony-forming potential
is profoundly impaired. AGM mesenchymal cells expressing Runx1, an essential
factor for definitive HSC specification, are almost absent in mutant mice. In
addition, hematopoietic clusters in the dorsal aorta, vitelline, and umbilical
arteries are reduced in size and number. These results show a requirement for
Meis1 in the establishment of definitive hematopoiesis in the mouse embryo.
Meis1 mutant mice also displayed complete agenesis of the megakaryocyte lineage
and localized defects in vascular patterning, which may cause the hemorrhagic
phenotype.

PMID: 15882575 [PubMed - indexed for MEDLINE]


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