Rearrangement in the breakpoint cluster region and the clinical course in Philadelphia-negative chronic myelogenous leukemia.
We have followed one patient with Philadelphia (Ph)-negative chronic myelogenous leukemia and identified an additional four patients from the literature who showed the rearrangement in the breakpoint cluster region (bcr) on chromosome 22 characteristic of Ph-positive chronic myelogenous leukemia. The clinical course of these five patients was similar to that of Ph-positive patients, with easily controlled leukocyte counts, a prolonged benign phase, and prolonged survival. Furthermore, we have shown, for the first time, that bcr rearrangement in Ph-negative chronic myelogenous leukemia can result in expression of the aberrant 210-kilodalton bcr-abl fusion protein, which has been strongly implicated in Ph-positive leukemogenesis. Research data pertaining to possible cytogenetic mechanisms leading to production of p210bcr-abl in the absence of the Ph chromosome are reviewed. Molecular analysis provides an important tool for classifying and predicting prognosis of some patients with Ph-negative chronic myelogenous leukemia.
D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure*; D002892:Chromosomes, Human, Pair 22 / Q000648:ultrastructure*; D002899:Chromosomes, Human, Pair 9 / Q000648:ultrastructure*; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009857:Oncogenes; D010677:Philadelphia Chromosome; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014178:Translocation, Genetic
D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl