Myeloid leukemia with promyelocytic features in transgenic mice expressing hCG-NuMA-RARα

Acute promyelocytic leukemia (APL) is characterized by the accumulation of abnormal promyelocytes in the bone marrow (BM), and by the presence of a reciprocal chromosomal translocation involving retinoic acid receptor alpha ( RARα ). To date, five RARα partner genes have been identified in APL. NuMA-RARα was identified in a pediatric case of APL carrying a translocation t(11;17)(q13;q21). Using a construct containing the NuMA-RARα fusion gene driven by the human cathepsin G promoter ( hCG-NuMA-RARα ), two transgenic mouse lines were generated. Transgenic mice were observed to have a genetic myeloproliferation (increased granulopoiesis in BM) at an early age, and rapidly developed a myeloproliferative disease-like myeloid leukemia. This leukemia was morphologically and immunophenotypically indistinguishable from human APL, with a penetrance of 100%. The phenotype of transgenic mice was consistent with a blockade of neutrophil differentiation. NuMA-RARα is therefore sufficient for disease development in this APL model.