| First Author | Li L | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 15 | Pages | 4116-4126 |
| PubMed ID | 28611040 | Mgi Jnum | J:244433 |
| Mgi Id | MGI:5913212 | Doi | 10.1158/0008-5472.CAN-17-0202 |
| Citation | Li L, et al. (2017) beta-Catenin Is a Candidate Therapeutic Target for Myeloid Neoplasms with del(5q). Cancer Res 77(15):4116-4126 |
| abstractText | Deletion of the chromosome 5q [del(5q)] is one of the most common cytogenetic abnormalities observed in patients with de novo myelodysplastic syndromes (MDS) and therapy-related MDS or acute myeloid leukemia (t-MDS/tAML). Emerging evidence indicates that activation of the Wnt/beta-catenin pathway contributes to the development of myeloid neoplasms with del(5q). Whether beta-catenin is a potential therapeutic target for myeloid neoplasms with del(5q) has yet to be evaluated. Here, we report that genetic deletion of a single allele of beta-catenin rescues ineffective hematopoiesis in an Apc haploinsufficient mouse model, which recapitulates several characteristic features of the preleukemic stage of myeloid neoplasms with a -5/del(5q). In addition, loss of a single allele of beta-catenin reversed the defective self-renewal capacity of Apc-haploinsufficient hematopoietic stem cells and reduced the frequency of apoptosis induced by Apc haploinsufficiency. Suppression of beta-catenin by indomethacin or beta-catenin shRNA reduced proliferation and survival of human leukemia cell lines with del(5q) but not of control leukemia cell lines in vitro; beta-catenin inactivation also inhibited leukemia progression in vivo in xenograft mice reconstituted with del(5q) leukemia cell lines. Inhibition of beta-catenin also stunted growth and colony-forming abilities of primary bone marrow cells from del(5q) AML patients in vitro Overall, our data support the idea that beta-catenin could serve as a therapeutic target for the treatment of myeloid neoplasms with del(5q). Cancer Res; 77(15); 4116-26. (c)2017 AACR. |
