The ABO antigen weakness is rarely observed in ABO typing for transfusion. Hematologic diseases and associated gene mutations have been suggested as potential causes of this phenomenon, yet the precise etiology has not been elucidated. Through ABO typing and genetic analysis data conducted over 7 years, we have reconfirmed the association between ABO antigen weakness and hematologic diseases, especially acute myeloid leukemia (odds ratio (OR) 2.55, 95% confidence interval (CI) 1.12-5.83) and myelodysplastic syndrome (OR 6.94, 95% CI 2.86-16.83), and discovered previously unidentified candidate genes, CEBPA (OR 43.70, 95% CI 18.12-105.40), NRAS (OR 3.37, 95% CI 1.46-7.79), U2AF1 (OR 8.12, 95% CI 2.86-23.03) and PTPN11 (OR 4.52, 95% CI 1.51-13.50), seemingly associated with this phenomenon. Among these, CEBPA double mutations displayed a significant association, with ABO antigen weakness being observed in 20 out of the 25 individuals (80.0%) possessing these mutations. From this study, new factors associated with ABO antigen weakness have been identified.