| First Author | Weidemann RR | Year | 2017 |
| Journal | Exp Hematol | Volume | 45 |
| Pages | 45-55.e6 | PubMed ID | 27664314 |
| Mgi Jnum | J:316244 | Mgi Id | MGI:6835318 |
| Doi | 10.1016/j.exphem.2016.09.005 | Citation | Weidemann RR, et al. (2017) Constitutive Kit activity triggers B-cell acute lymphoblastic leukemia-like disease in mice. Exp Hematol 45:45-55.e6 |
| abstractText | Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and, in most cases, is of pro- or pre-B cell origin (B-ALL). The receptor tyrosine kinase KIT is expressed by hematopoietic stem and precursor cells. Gain-of-function mutations of KIT cause systemic mastocytosis, which is characterized by abnormal accumulations of mast cells. We previously reported a mouse model of mastocytosis based on conditional expression of a constitutively active Kit protein. Half of these animals developed leukemic disease of B-lineage origin. Herein, we report that this condition bears striking similarities to human B-ALL. The immuno-phenotype of the leukemic cells was compatible with a pro-B-cell origin, as was the finding of immunoglobulin heavy-chain gene rearrangements in all cases, whereas light-chain loci were mostly not rearranged. Leukemogenesis was independent of pre-B-cell receptor expression. Primary leukemic cells and permanent cell lines derived from these were serially transplantable and rapidly killed the recipients. In a few animals, the leukemia was of T-cell origin with abnormal CD4/8 double-positive T-cell precursors dominating in the circulation. In summary, we report a novel ALL mouse model that may prove useful for in vivo drug testing and identification of novel oncogenic mutations and principles. |
