ABSTRACT
Noncoding somatic mutations have been demonstrated to play important role in tumourigenesis. Here we show that there exists an acute myeloid leukaemia associated noncoding somatic mutation at 3′ terminal of conserved HOXA cluster. The mutation was identified in the bone marrow blasts but not peripheral blood mononuclear cells or buccal cells of two M3 (acute promyelocytic leukaemia, APL) type patients from 45 acute myeloid leukaemia patients. The mutation also existed in a pair of twins one of them developed acute myeloid leukaemia M4 (acute myelomonocytic leukaemia) type. The mutation resides in about 2-kb downstream of HOXA1 gene where a functional retinoic acid response element is located and also bound by histone demethylase KDM3B. Reporter assay showed that the mutation results in the upregulation of transcriptional activity and unresponsiveness to retinoic acid receptor. To sum up, we identified a new acute myeloid leukaemia associated noncoding somatic mutation.