X-linked clonal analysis (XLCA) either using Glucose-6-phosphate dehydrogenase (G-6-P-D) polymorphisms or restriction fragment length polymorphisms (RFLP) and methylation analysis has provided considerable understanding of haematologic malignancy. Acute Promyelocytic Leukemia (APL) is characterized by a unique cytogenetic translocation t(15;17), frequent achievement of remission without a preceding phase of marrow hypocellularity after induction chemotherapy and a high rate of clinical response to all-trans retinoic acid (ATRA). In limited studies XLCA has provided insight into the pathogenesis and mechanism of drug action in this disease.