| First Author | Ko RM | Year | 2008 |
| Journal | Leuk Res | Volume | 32 |
| Issue | 7 | Pages | 1101-11 |
| PubMed ID | 18037485 | Mgi Jnum | J:349132 |
| Mgi Id | MGI:7646067 | Doi | 10.1016/j.leukres.2007.10.012 |
| Citation | Ko RM, et al. (2008) Roles of p15Ink4b and p16Ink4a in myeloid differentiation and RUNX1-ETO-associated acute myeloid leukemia. Leuk Res 32(7):1101-11 |
| abstractText | Inactivation of p15(Ink4b) expression by promoter hypermethylation occurs in up to 80% of acute myeloid leukemia (AML) cases and is particularly common in the FAB-M2 subtype of AML, which is characterized by the presence of the RUNX1-ETO translocation in 40% of cases. To establish whether the loss of p15(Ink4b) contributes to AML progression in association with RUNX1-ETO, we have expressed the RUNX1-ETO fusion protein from a retroviral vector in hematopoietic progenitor cells isolated from wild-type, p15(Ink4b) or p16(Ink4a) knockout bone marrow. Analysis of lethally irradiated recipient mice reconstituted with RUNX1-ETO-expressing cells showed that neither p15(Ink4b) or p16(Ink4a) loss significantly accelerated disease progression over the time period of one year post-transplantation. Loss of p15(Ink4b) alone resulted in increased myeloid progenitor cell frequencies in bone marrow by 10-month post-transplant and a 19-fold increase in the frequency of Lin(-)c-Kit(+)Sca-1(+) (LKS) cells that was not associated with expansion of long-term reconstituting HSC. These results strongly suggest that p15(Ink4b) loss must be accompanied by additional oncogenic changes for RUNX1-ETO-associated AML to develop. |
