Eintrag weiter verarbeiten
Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model
Gespeichert in:
Personen und Körperschaften: | , , , , , , , , , |
---|---|
Titel: |
Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model |
In: | Blood, 105, 2005, 2, S. 784-793 |
veröffentlicht: |
American Society of Hematology
|
Umfang: | 784-793 |
ISSN: |
0006-4971 1528-0020 |
DOI: | 10.1182/blood-2004-04-1508 |
Zusammenfassung: | <jats:title>Abstract</jats:title><jats:p>The chromosomal translocation t(7; 11)(p15;p15), observed in human myeloid leukemia, results in a NUP98 and HOXA9 gene fusion. We generated a transgenic mouse line that specifically expressed the chimeric NUP98-HOXA9 gene in the myeloid lineage. While only 20% of the transgenic mice progressed to leukemia after a latency period, myeloid progenitor cells from nonleukemic transgenic mice still exhibited increased proliferative potential. This suggested that the NUP98-HOXA9 fusion induced a preleukemic phase, and other factors were required for complete leukemogenesis. NUP98-HOXA9 expression promoted the onset of retrovirus-induced BXH2 myeloid leukemia. This phenomenon was used to identify cooperative disease genes as common integration sites (CISs). Meis1, a known HOX cofactor, was identified as a CIS with a higher integration frequency in transgenic than in wild-type BXH2 mice. By the same means we identified further 4 candidate cooperative genes, Dnalc4, Fcgr2b, Fcrl, and Con1. These genes cooperated with NUP98-HOXA9 in transforming NIH 3T3 cells. The system described here is a powerful tool to identify cooperative oncogenes and will assist in the clarification of the multistep process of carcinogenesis.</jats:p> |
Format: | E-Article |
Quelle: | American Society of Hematology (CrossRef) |
Sprache: | Englisch |