The tumor suppressor Ikaros transcription factor is crucial for the anti‐proliferative Vasoactive Intestinal Peptide Receptor‐1 expression in developing thymocytes

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The Leukemia and Lymphoma Society states more children die of leukemia yearly than any other cancer, therefore effective treatments are crucial. In the absence of the tumor suppressor Ikaros (IK), mice develop T cell leukemia with 100% penetrance. We demonstrated that IK regulates a gene termed vasoactive intestinal peptide receptor‐1 (VPACR‐1), when overexpressed in NIH‐3T3 cells. In T cells, VPACR‐1 suppresses interleukin‐2 and subsequent proliferation. Therefore, we hypothesize that IK tumor suppressor activities are manifested by maintaining high levels of VPACR‐1. Thus, an IK null, double negative stage 3 (DN3) thymocyte cell line, JE131, showed a significant reduction in VPACR‐1 compared to wild type (WT) thymic tissue. To obtain an accurate comparison to JE131 cells, thymic tissue was purified by AutoMACS and FACS for the DN3 subpopulation with a similar phenotype to JE131 cells (CD44Lo/CD25Hi/CD4−/CD8−). By qPCR, WT DN3s expressed VPACR‐1 ≤20% that of total DN cells, however this low level is ≥16X that of JE131 cells, and strongly supports IK as a positive potentiator for thymocyte VPACR‐1 expression. Future studies will reintroduce IK into JE131 cells by lentiviral transduction to rescue VPACR‐1 expression and support VPACR‐1 as an IK gene target. Another major goal is to map VPACR‐1 expression levels in all DN populations. Supported by NIH/NIDDK Career Award (KO1 5K01DK64828‐2) and COBRE at NDSU.