Leukemia  1994 Aug;8(8):1331-6 

N-ras mutation and karyotypic evolution are closely associated with leukemic
transformation in myelodysplastic syndrome.

Horiike S, Misawa S, Nakai H, Kaneko H, Yokota S, Taniwaki M, Yamane Y, Inazawa
J, Abe T, Kashima K.

Department of Internal Medicine, III, Kyoto Prefectural University of Medicine,
Japan.

We performed a longitudinal analysis of the karyotypes and N-ras gene
configuration of bone marrow cells in 35 patients with myelodysplastic syndrome
(MDS). Karyotypic evolution was found in eight patients, and was associated with
disease progression, including leukemic transformation, in all the patients. We
identified N-ras mutations in six patients, using a polymerase chain reaction
(PCR) technique, in which oligonucleotide primers were constructed with induced
mismatches, followed by endonuclease digestion. Direct sequencing confirmed
single base substitutions at codon 12 in two patients and at codon 13 in four.
The incidence of N-ras gene mutations was significantly higher in the
karyotypically evolved group (five of eight patients) than in the stable group
(one of 27 patients). All of five patients harboring both karyotypic evolution
and an N-ras mutation showed concomitant disease progression to overt leukemia
or refractory anemia with excess of blasts in transformation (RAEB-T). Two of
four patients with either karyotypic evolution or N-ras mutation and six of 26
patients without any of these alterations also progressed to overt leukemia. Our
results indicate that the accumulation of these genetic alterations is closely
associated with leukemic transformation of MDS, although other genetic
alterations may also play a key role in the remaining patients.

PMID: 8057669 [PubMed - indexed for MEDLINE]