| Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia,which is morphologically characterized by a clear differentiation block of the granulocytic lineage at the promyelocytic stage. More than 95% of APL patients have PML-RARαfusion gene resulting from the t(15;17) chromosomal translocation, about 2% have PLZF-RARαand RARα-PLZF fusion genes generated by the t(15;17) chromosomal translocation.We establish three kinds of APL retroviral mouse models: PML-RARα, PLZF- RARαand PLZF-RARα/RARα-PLZF by ex vivo retroviral transduction and bone marrow transplantation, the three kinds of mice all develop human APL-like disease. Leukemia mice present abnormal peripheral blood and massive splenohepatomegaly due to leukemic cells infiltration. The cell population of the granulocytic lineage mainly consisting of promyelocyte is increased significantly in bone marrow, and the leukemic cells simultaneously express myeloid lineage markers Gr-1 and Mac-1, as well as progenitor markers CD34 and c-Kit. The median latency of PML-RARαand PLZF-RARα/RARα-PLZF mice is about 5 months, while 7 months for PLZF-RARαmice. The three kinds of leukemia are transplantable and recipient mice developed APL with shorter latency. ATRA prolonged lifespan of PML-RARαleukemia mice, while PLZF-RARα/RARα-PLZF leukemia mice were insensitive to ATRA.The three kinds of APL retroviral transduction mouse models established by us may provide the platform for further investigations on the pathological mechanism and clinical interference of APL. |
