RCH-ACV

Disease-inducing Potential of a Leukemic Cell Line (RCH-ACV) in a Xenografting Model

Ovarian failure is common among cancer survivors due to gonadotoxic treatment modalities like chemotherapy and radiotherapy. Ovarian tissue cryopreservation and transplantation is an emerging fertility restoration modality for such patients. However, leukemia patients are at a constant threat of re-introducing malignant cells through transplantation of their cryopreserved ovarian tissues. Manavella et al. studied the tumor-inducing potential of leukemic cell lines RCH-ACV xenografted to immunodeficient mice, in order to estimate the relapse risk after transplantation of ovarian tissues in leukemia patients. 54 female immunodeficient mice were grafted with 100, 200, 500, 1000 or 10,000 RCH-ACV cells, along with human ovarian stromal cells (50,000), embedded in a fibrin scaffold. Mice grafted with 100 RCH-ACV cells showed no signs of disease, while those with 200 cells had peritoneal masses and liver invasion. All mice with 500, 1000, or 10,000 cells developed liver invasion and tumors. Since the extent of macroscopic lesions in RCH-ACV cell line were too large, histological confirmation of liver samples from RCH-ACV grafted mice were taken and processed. Histological slides showed clear leukemic infiltration (Fig.1).

Loss of p53 Impairs Death Receptor Expression and Confers Resistance to CD19 CAR T-Cell Therapy in BCP-ALL

Relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with TP53 mutations has a poor prognosis. CAR T therapy is approved for relapsed/refractory BCP-ALL, but patients with TP53 mutations show worse outcomes. Cox et al. investigated how p53 loss affects CAR T therapy response and identify potential ways to improve treatment efficacy for both TP53-mutated and wild-type BCP-ALL patients.

To test whether there is a cell-intrinsic resistance to CAR T as a result of p53 loss, they aimed to recapitulate diminished CAR T efficacy in an in vitro killing assay. They combined isogenic TP53^WT and TP53^Mut fluorescent models of the BCP-ALL cell lines Nalm6 and RCH-ACV in a 1:1 ratio and challenged them with either untransduced or CART19 cells to test for competitive survival. Both cell lines were targeted by CAR T, (Fig. 2A) and for both models, the TP53^Mut population showed a survival advantage over the wild-type controls when treated with CART19 cells (Fig. 2B), indicating that CART19 treatment is less effective against TP53^Mut BCP-ALL.