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N-ras mutations are associated with poor prognosis and increased risk of
leukemia in myelodysplastic syndrome
RL Paquette, EM Landaw, RV Pierre, J Kahan, M Lubbert, O Lazcano, G Isaac, F McCormick and HP Koeffler
Division of Hematology/Oncology, UCLA School of Medicine.
To evaluate the clinical significance of N-ras mutations in the
myelodysplastic syndrome (MDS) archival bone marrow samples from 252
patients were studied for the presence of N-ras exon I mutations using
polymerase chain reaction amplification and differential oligonucleotide
hybridization. Subsequently, clinical information about these patients was
obtained and analyzed. Of 220 evaluable patients, 20 (9%) had point
mutation of N-ras involving codon 12. Individuals with N- ras mutation had
a significantly shorter survival period than those who were N-ras negative
(P = .02). An increased risk of acute myelogenous leukemia (AML) was also
found in patients with N-ras mutations (P = .005). N-ras mutations were not
associated with any French-American- British (FAB) subtype, with the
presence of increased myeloblasts, or with chromosomal aberrations in the
bone marrow. However, the presence of increased bone marrow blasts was
strongly associated with poor survival rate and risk of AML (P < .001
for each). After stratifying for the percentage of blasts, N-ras mutations
remained significantly associated with shorter survival period (P = .04)
and increased risk of AML (P = .02). Bone marrow cytogenetic abnormalities,
particularly when multiple abnormalities were present, were significantly
associated with a poor prognosis (P < .001). In conclusion, N-ras
mutation, although relatively infrequent in MDS, is associated with short
survival period and increased probability of developing AML.
Volume 82,
Issue 2,
pp. 590-599,
07/15/1993
Copyright © 1993 by The American Society of Hematology
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