| First Author | Churchman ML | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 5 | Pages | 937-948.e8 |
| PubMed ID | 29681510 | Mgi Jnum | J:261863 |
| Mgi Id | MGI:6156726 | Doi | 10.1016/j.ccell.2018.03.021 |
| Citation | Churchman ML, et al. (2018) Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia. Cancer Cell 33(5):937-948.e8 |
| abstractText | Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Here we report coding germline IKZF1 variation in familial childhood ALL and 0.9% of presumed sporadic B-ALL, identifying 28 unique variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. These results identify IKZF1 as a leukemia predisposition gene, and emphasize the importance of germline genetic variation in the development of both familial and sporadic ALL. |
