PMID- 12515728
OWN - NLM
STAT- MEDLINE
DCOM- 20030618
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 8
DP  - 2003 Apr 15
TI  - Prenatal and postnatal myeloid cells demonstrate stepwise progression in the 
      pathogenesis of MLL fusion gene leukemia.
PG  - 3229-35
AB  - The steps to leukemia following an in utero fusion of MLL (HRX, ALL-1) to a 
      partner gene in humans are not known. Introduction of the Mll-AF9 fusion gene 
      into embryonic stem cells results in leukemia in mice with cell-type specificity 
      similar to humans. In this study we used myeloid colony assays, 
      immunophenotyping, and transplantation to evaluate myelopoiesis in Mll-AF9 mice. 
      Colony assays demonstrated that both prenatal and postnatal Mll-AF9 tissues have 
      significantly increased numbers of CD11b(+)/CD117(+)/Gr-1(+/-) myeloid cells, 
      often in compact clusters. The self-renewal capacity of prenatal myeloid 
      progenitors was found to decrease following serial replating of colony-forming 
      cells. In contrast, early postnatal myeloid progenitors increased following 
      replating; however, the enhanced self-renewal of early postnatal myeloid 
      progenitor cells was limited and did not result in long-term cell lines or 
      leukemia in vivo. Unlimited replating, long-term CD11b/Gr-1(+) myeloid cell 
      lines, and the ability to produce early leukemia in vivo in transplantation 
      experiments, were found only in mice with overt leukemia. Prenatal Mll-AF9 
      tissues had reduced total (mature and progenitor) CD11b/Gr-1(+) cells compared 
      with wild-type tissues. Colony replating, immunophenotyping, and cytochemistry 
      suggest that any perturbation of cellular differentiation from the prenatal stage 
      onward is partial and largely reversible. We describe a novel informative in 
      vitro and in vivo model system that permits study of the stages in the 
      pathogenesis of Mll fusion gene leukemia, beginning in prenatal myeloid cells, 
      progressing to a second stage in the postnatal period and, finally, resulting in 
      overt leukemia in adult animals.
FAU - Johnson, Jennifer J
AU  - Johnson JJ
AD  - University of Minnesota Cancer Center, Minneapolis, MN 55455, USA.
FAU - Chen, Weili
AU  - Chen W
FAU - Hudson, Wendy
AU  - Hudson W
FAU - Yao, Qing
AU  - Yao Q
FAU - Taylor, Marnie
AU  - Taylor M
FAU - Rabbitts, Terence H
AU  - Rabbitts TH
FAU - Kersey, John H
AU  - Kersey JH
LA  - eng
GR  - CA49721/CA/NCI NIH HHS/United States
GR  - CA87053/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20021219
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (MLL-AF9 fusion protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Bone Marrow/embryology/growth & development
MH  - Bone Marrow Transplantation
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Cellular Senescence
MH  - Colony-Forming Units Assay
MH  - Disease Progression
MH  - Embryo, Mammalian/cytology
MH  - Exons/genetics
MH  - Female
MH  - Gene Targeting
MH  - Gestational Age
MH  - Hematopoietic System/embryology/growth & development
MH  - Humans
MH  - Immunophenotyping
MH  - Leukemia, Experimental/etiology/genetics/*pathology
MH  - Liver/embryology/growth & development
MH  - Male
MH  - Mice
MH  - Models, Biological
MH  - Mutagenesis, Insertional
MH  - Myeloid Cells/*pathology
MH  - Myeloid-Lymphoid Leukemia Protein
MH  - Oncogene Proteins, Fusion/genetics/*physiology
MH  - Organ Specificity
MH  - Radiation Chimera
MH  - Stem Cells/cytology
EDAT- 2003/01/08 04:00
MHDA- 2003/06/19 05:00
CRDT- 2003/01/08 04:00
PHST- 2003/01/08 04:00 [pubmed]
PHST- 2003/06/19 05:00 [medline]
PHST- 2003/01/08 04:00 [entrez]
AID - S0006-4971(20)50825-2 [pii]
AID - 10.1182/blood-2002-05-1515 [doi]
PST - ppublish
SO  - Blood. 2003 Apr 15;101(8):3229-35. doi: 10.1182/blood-2002-05-1515. Epub 2002 Dec 
      19.