Altered Myeloid Development and Acute Leukemia in Transgenic Mice Expressing PML-RARα Under Control of Cathepsin G Regulatory Sequences

摘要: Acute promyelocytic leukemia (APML) is characterized by abnormal myeloid development, resulting an accumulation of leukemic promyelocytes that are often highly sensitive to retinoic acid. A balanced t(15;17) (q22;q21) reciprocal chromosomal translocation found in approximately 90% APML patients; this fuses the PML gene on chromosome 15 acid receptor alpha (RAR alpha) 17, creating two novel fusion genes, PML-RAR and RAR alpha-PML. The product, which expressed virtually all patients with t(15;17), thought play a direct role pathogenesis APML. To determine whether sufficient cause animal model, we used promyelocyte-specific targeting sequences human cathepsin G (hCG) expression cDNA early cells transgenic mice. Mice expressing hCG-PML-RAR transgene were have altered development was increased percentages immature mature peripheral blood, bone marrow, spleen. In addition, 30% transgene-expressing mice eventually developed acute after long latent period. splenic both nonleukemic phenotypes responded all-trans (ATRA) treatment, caused apoptosis precursors. Although low-level not directly mice, its alters precursors may be susceptible cooperative transforming events.