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

Shigeo Horiike, Shinichi Misawa, Hiroyuki Nakai, Hiroto Kaneko, Shohei Yokota, Masafumi Taniwaki, Yoko Yamane, Johji Inazawa, Tatsuo Abe, Kei Kashima

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1331-1336
Number of pages6
JournalLeukemia
Volume8
Issue number8
StatePublished - Aug 1994

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'N-ras mutation and karyotypic evolution are closely associated with leukemic transformation in myelodysplastic syndrome'. Together they form a unique fingerprint.

  • Cite this

    Horiike, S., Misawa, S., Nakai, H., Kaneko, H., Yokota, S., Taniwaki, M., Yamane, Y., Inazawa, J., Abe, T., & Kashima, K. (1994). N-ras mutation and karyotypic evolution are closely associated with leukemic transformation in myelodysplastic syndrome. Leukemia, 8(8), 1331-1336.