Sequential relapses of blastic crisis may involve different clones of cells with different molecular abnormalities.
A patient with typical Ph1-positive CML was studied during sequential phases: (1) initial chronic phase, (2) first myeloid blast crisis, (3) second chronic phase, and (4) accelerated disease leading to a second blast crisis. A point mutation in codon 239 of the p53 gene and a novel chromosome 17 alteration appeared concomitantly with the first blast crisis and then disappeared with re-establishment of a second chronic phase. They did not reappear with the second acute phase, indicating that the clone responsible for the original blast crisis had been suppressed and supplanted by another clone of malignant cells. This observation suggests that in at least some CML patients drug therapy can suppress or eliminate an aggressive malignant cell clone, but that the underlying molecular defect in haemopoietic cells (in this case the c-ABL translocation) persists and other aggressive clones with different molecular lesions eventually arise. Our observations and inferences are consistent with the hypothesis advanced by Fialkow et al (1991) to explain clonal remissions in acute non-lymphocytic leukaemia.
Foti
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UCLA Department of Medicine, 90024.
Cline
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MJ
D000328:Adult; D001483:Base Sequence; D001752:Blast Crisis / Q000235:genetics*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D002999:Clone Cells; D005091:Exons; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D012008:Recurrence