Upon Aza+HAG treatment, we observed the high CR/CRi rate in ND patients with mutated BCOR (100%,7/7), KIT (100%,3/3), IDH1 (100%,7/7), NPM1 (93.3%,14/15), ASXL1 (88.9%,8/9), DNMT3A (80. 0%,16/20), RUNX1 (75.0%,6/8), FLT3 (71.4%,5/7), and TET2 (71.4%,10/14) (Fig. 1I). We further observed the clearance of mutated genes after the induction therapy and found the variant allele fraction (VAF) of mutants was dramatically reduced among the CR/CRi patients. Specifically, VAF change of FLT3 mutant from 3 of 4 available patients reduced to <0.01%, with the other one, decreased by 91.9% (Fig. 1J); 4 out of 6 patients with IDH1 mutant reduced to <0.01%, with the other two, decreased 67.6% and 35.9%, respectively (Fig. 1K); 5 out of 6 patients with ASXL1 mutant reduced to <0.01%, with the other one, decreased by 33.4% (Fig. 1L); and 10 out of 14 patients with NPM1 mutant reduced to <0.01%, respectively (Fig. 1M). This study demonstrated that the Aza+HAG regimen is a cost-effective first-line therapy with high efficacy and well tolerance for elderly/unfit AML, especially ND AML patients.