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>