Our studies suggest that ALDHi [disulfiram, FDA-approved drug for the treatment of alcoholism [41] and/or ADH5i [N6022, evaluated against pulmonary emphysema and asthma [58, 59] should enhance the anti-leukemic effect of Polθi in cohorts of HR-deficient acute leukemias and in OTK-positive myeloid malignancies (AML and MPN) which accumulate high levels of endogenously produced formaldehyde [10, 35]. Here, POLI is linked to myeloproliferative disorder.