As HOXA4 protein is a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation, it is reasonable to suggest that the suppression of HOXA4 protein production by hypermethylation induced gene silencing could be one of the potential mechanisms in BCR-ABL-independent pathway that promote IM resistance in CML patients. The gene discussed is HOXA4; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.