Effect of ADAR1 on the development of MLL-AF9 induced murine AML / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To establish the ADAR1 (adenosine deaminase that act on RNA 1) knockout MLL-AF9 acute myeloid leukemia (AML) mouse model, and to preliminarily investigate the effects of ADAR1 deletion on the development of AML.</p><p><b>METHODS</b>The lineage⁻ (Lin⁻) cells of ER-CreADAR1(lox/lox) mice and their ADAR1(lox/lox) counterparts were enriched by magnetic activated cell sorting (MACS) and then transduced with retrovirus carrying MSCV- MLL/AF9-IRES-GFP fusion gene. The efficiency of transduction was detected by flow cytometry, and equal number of GFP⁺ cells were transplanted into lethally irradiated recipient mice. The recipient mice were treated with tamoxifen at 48 hours after transplantation to induce ADAR1 knockout and divided into following groups experimental group (ER-Cre;ADAR1(lox/lox)+tamoxifen), control groups ((1)ER-Cre;ADAR1(lox/lox)+vechile, (2)ADAR1(lox/lox)+tamoxifen, (3)ADAR1(lox/lox)+vechile). The percentage of GFP⁺ cells in peripheral blood was examined at 10, 15 and 20 days respectively after transplantation and the survival of the recipient mice was observed. In vitro study, ER-Cre;ADAR1(lox/lox) and ADAR1(lox/lox) AML cells were cultured and the apoptosis rates of these cells 48 hours after 4-hydroxytamoxifen treatment were examined.</p><p><b>RESULTS</b>The ADAR1 deletion MLL-AF9 AML mouse model was successfully established. Deletion of ADAR1 could decrease the percentage of GFP⁺ cells in the peripheral blood and significantly prolong the survival rate of recipient mice（P<0.05）. In vitro study showed that the cultured total cell number, percentage of GFP⁺ cells decreased and the apoptosis rate of AML cells increased.</p><p><b>CONCLUSION</b>Ablation of ADAR1 could delay the progression of AML in recipient mice. ADAR1 plays a critical role in the development and maintenance of murine MLL-AF9 AML.</p>