| First Author | Seo JH | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 18 | Pages | 7325-35 |
| PubMed ID | 20807813 | Mgi Jnum | J:164209 |
| Mgi Id | MGI:4830906 | Doi | 10.1158/0008-5472.CAN-10-0607 |
| Citation | Seo JH, et al. (2010) A specific need for CRKL in p210BCR-ABL-induced transformation of mouse hematopoietic progenitors. Cancer Res 70(18):7325-35 |
| abstractText | CRKL (CRK-like) is an adapter protein predominantly phosphorylated in cells that express the tyrosine kinase p210(BCR-ABL), the fusion product of a (9;22) chromosomal translocation causative for chronic myeloid leukemia. It has been unclear, however, whether CRKL plays a functional role in p210(BCR-ABL) transformation. Here, we show that CRKL is required for p210(BCR-ABL) to support interleukin-3-independent growth of myeloid progenitor cells and long-term outgrowth of B-lymphoid cells from fetal liver-derived hematopoietic progenitor cells. Furthermore, a synthetic phosphotyrosyl peptide that binds to the CRKL SH2 domain with high affinity blocks association of endogenous CRKL with the p210(BCR-ABL) complex and reduces c-MYC levels in K562 human leukemic cells as well as in mouse hematopoietic cells transformed by p210(BCR-ABL) or the imatinib-resistant mutant T315I. These results indicate that the function of CRKL as an adapter protein is essential for p210(BCR-ABL)-induced transformation. |
