Mutations of the ras protooncogenes in chronic myelogenous leukemia: a high
frequency of ras mutations in bcr/abl rearrangement-negative chronic
myelogenous leukemia
PC Cogswell, R Morgan, M Dunn, A Neubauer, P Nelson, NK Poland-Johnston, AA Sandberg and E Liu
Department of Medicine, University of North Carolina, Chapel Hill 27599.
Seventy cases of chronic myelogenous leukemia (CML) were analyzed for the
presence of ras mutations using polymerase chain reaction (PCR),
oligonucleotide hybridization, and direct PCR sequencing. All cases had
preceding cytogenetic and bcr rearrangement studies. Aberrant ras genes
were detected in none of 39 patients with Philadelphia (Ph) chromosome or
bcr/abl rearrangement positive chronic-phase CML and in only 1 of 18
patients in blast crisis, suggesting that ras mutations have little or no
role in initiation or progression of common CML. Seven of 13, or 54% of
patients with bcr/abl rearrangement negative chronic phase CML (atypical
CML) harbored mutations in ras, however. This high incidence of ras
mutations, together with the absence of bcr/abl rearrangement, provides
evidence that atypical CML is an entity that is molecularly distinct from
common CML. Moreover, the clinical characteristics and the high frequency
of ras mutations suggest that atypical CML may constitute a subset of the
myelodysplastic syndrome and may be best classified as a variant of chronic
myelomonocytic leukemia (CMML).
Volume 74,
Issue 8,
pp. 2629-2633,
12/01/1989
Copyright © 1989 by The American Society of Hematology
