We sequentially analyzed the immunoglobulin heavy chain (IgH) variable region gene of leukemia cells obtained from a chronic myeloid leukemia (CML) patient who had three episodes of B-lymphoid crisis after bone marrow transplantation. Southern blots using the JH probe showed a single rearranged band which differed at each crisis, although the rearranged bands of the BCR gene were the same at each crisis. The IgH variable region sequences of the leukemia cells at each crisis were different. These observations suggested that multiple clones were generated from the progenitor cells of the blast crisis, which were transformed at a very early stage of B-lymphocyte ontogeny.