AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency.
The translocation (8;21), generating the AML1-ETO fusion protein, is one of the most frequent chromosomal abnormalities associated with acute myelogenous leukemia (AML). To elucidate its role in oncogenesis, bone marrow (BM) cells were infected with a retroviral vector carrying AML1-ETO and transplanted into mice. In contrast to previous transgenic mouse models, we show that AML1-ETO directly stimulates granulopoiesis, suppresses erythropoiesis, and impairs the maturation of myeloid, B, and T lymphoid cells in vivo. To determine the significance of earlier findings that expression of the tumor suppressor ICSBP is often downregulated in AML myeloblasts, AML1-ETO was introduced into BM cells derived from mice lacking the interferon regulatory factor ICSBP. Our findings demonstrate that AML1-ETO synergizes with an ICSBP deficiency to induce myeloblastic transformation in the BM, reminiscent of AML.
Schwieger
Maike
M
Department of Cell and Virus Genetics, Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, D-20251 Hamburg, Germany.
Löhler
Jürgen
J
Friel
Jutta
J
Scheller
Marina
M
Horak
Ivan
I
Stocking
Carol
C
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D019070:Cell Lineage; D050676:Core Binding Factor Alpha 2 Subunit; D004920:Erythropoiesis; D015870:Gene Expression; D005822:Genetic Vectors; D006410:Hematopoiesis / Q000502:physiology*; D050835:Interferon Regulatory Factors; D038041:Lymphopoiesis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D000075142:RUNX1 Translocation Partner 1 Protein; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012190:Retroviridae; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic; D000099185:Interferon Regulatory Factor-8
D050676:Core Binding Factor Alpha 2 Subunit; D050835:Interferon Regulatory Factors; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D012097:Repressor Proteins; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; C107844:AML1-ETO fusion protein, human