Reversibility of acute B-cell leukaemia induced by BCR-ABL1.
Cancer is thought to arise from multiple genetic events that establish irreversible malignancy. A different mechanism might be present in certain leukaemias initiated by a chromosomal translocation. We have taken a new approach to determine if ablation of the genetic abnormality is sufficient for reversion by generating a conditional transgenic model of BCR-ABL1 (also known as BCR-ABL)-induced leukaemia. This oncogene is the result of a reciprocal translocation and is associated with different forms of leukaemia. The most common form, p210 BCR-ABL1, is found in more than 90% of patients with chronic myelogenous leukaemia (CML) and in up to 15% of adult patients with de novoacute lymphoblastic leukaemia (ALL). Efforts to establish a useful transgenic model have been hampered by embryonic lethality when the oncogene is expressed during embryogenesis, by reduced penetrance or by extremely long latency periods. One model uses the 'knock-in' approach to induce leukaemia by p190 BCR-ABL1(ref. 10). Given the limitations of models with p210, we used a different experimental approach. Lethal leukaemia developed within an acceptable time frame in all animals, and complete remission was achieved by suppression of BCR-ABL1expression, even after multiple rounds of induction and reversion. Our results demonstrate that BCR-ABL1is required for both induction and maintenance of leukaemia.
Huettner
C S
CS
Hematology/Oncology Division, Harvard Institutes of Medicine and Harvard Medical School, Boston, Massachusetts, USA.
Zhang
P
P
Van Etten
R A
RA
Tenen
D G
DG
D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D002051:Burkitt Lymphoma / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation
D016044:Fusion Proteins, bcr-abl