Overexpression of stem cell associated ALDH1A1, a target of the leukemogenic transcription factor TLX1/HOX11, inhibits lymphopoiesis and promotes myelopoiesis in murine hematopoietic progenitors.
TLX1/HOX11 is an oncogenic transcription factor in human T-cell leukemia, however, the molecular basis for its transforming activity has remained elusive. The ALDH1A1 gene, whose product participates in retinoic acid synthesis, was previously identified as a TLX1-responsive gene. Here, we confirm regulation of ALDH1A1 transcription by TLX1 and show that ALDH1A1 can profoundly perturb murine hematopoiesis by promoting myeloid differentiation at the expense of lymphopoiesis. Together, these data demonstrate that ALDH1A1 plays a key role in normal hematopoiesis, and confirm ALDH1A1 as a TLX1 transcriptional target that may contribute to the ability of this homeoprotein to alter cell fate and induce tumor growth.
Rice
Kim L
KL
School of Veterinary and Biomedical Sciences, Division of Health Sciences, Murdoch University, South Street, Murdoch, Perth WA 6150, Australia.
Izon
David J
DJ
Ford
Jette
J
Boodhoo
Alvin
A
Kees
Ursula R
UR
Greene
Wayne K
WK
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015152:Blotting, Northern; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism / Q000473:pathology*; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D038042:Myelopoiesis / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D017931:DNA Primers; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C071250:TLX1 protein, human; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase