Genomic alterations involving the c-myc proto-oncogene locus during the evolution of a case of chronic granulocytic leukaemia

Abstract

In a patient with Ph-positive chronic granulocytic leukaemia who had 3 separate episodes of promyelocytic transformation associated with new cytogenetic and genetic changes DNA from the peripheral-blood leucocytes obtained during the second episode of transformation showed an 8-fold to 16-fold amplification of cellular myc proto-oncogene (c-myc) sequences, and rearrangement of these sequences. There was no amplification or rearrangement of c-myc sequences in DNA from leucocytes collected during the chronic phase, nor were these sequences amplified in DNA from leucocytes collected during the third episode of transformation. These observations show that new clones of cells that proliferate during the evolution of a myeloid leukaemia can carry genetic changes in addition to any recognisable karyotypic changes. Such genetic changes might underlie the progression of the disease.