Murine acute promyelocytic leukemia cells can be recognized and cleared in vivo by adaptive immune mechanisms.

Background And Objectives: In this study, we tested whether transgenic murine acute promyelocytic leukemia (APL) cells can be recognized and cleared by adaptive immune responses and/or vaccination strategies.

Design And Methods: Immunocompetent and SCID mice were examined for their ability to survive a challenge of APL cells. We also vaccinated immunocompetent mice with DNA vaccines encoding various portions of a bcr-1 PML-RARa fusion protein.

High-penetrance mouse model of acute promyelocytic leukemia with very low levels of PML-RARalpha expression.

Transgenic mice expressing PML-RARalpha in early myeloid cells under control of human cathepsin G regulatory sequences all develop a myeloproliferative syndrome, but only 15% to 20% develop acute promyelocytic leukemia (APL) after a latent period of 6 to 14 months. However, this transgene is expressed at very low levels in the bone marrow cells of transgenic mice. Because the transgene includes only 6 kb of regulatory sequences from the human cathepsin G locus, we hypothesized that sequences required for high-level expression of the transgene might be located elsewhere in the cathepsin G locus and that a knock-in model might yield much higher expression levels and higher penetrance of disease.

Adaptive immunity cooperates with liposomal all-trans-retinoic acid (ATRA) to facilitate long-term molecular remissions in mice with acute promyelocytic leukemia.

We previously developed a murine model of acute promyelocytic leukemia (APL) by using human cathepsin G gene regulatory elements to direct the expression of promyelocytic leukemia (PML)/retinoic acid receptor alpha (RAR alpha) and RAR alpha/PML fusion cDNAs to the early myeloid compartment of transgenic mice. To study the efficacy of noncytotoxic therapy in this animal model, cohorts of naive immunocompetent mice were inoculated with primary murine APL cells from a frozen tumor bank. Arsenic trioxide and liposomally encapsulated all-trans-retinoic acid (Lipo ATRA), alone or in combination, were administered for 21 days by i.