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Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia.

Publication ,  Journal Article
Neubauer, A; Dodge, RK; George, SL; Davey, FR; Silver, RT; Schiffer, CA; Mayer, RJ; Ball, ED; Wurster-Hill, D; Bloomfield, CD
Published in: Blood
March 15, 1994

Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12, 13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells, ras mutations were detected by an algorithm based on allele-specific oligonucleotide hybridization. Eighteen of 99 (18%) patients harbored mutations in either N- or K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both N- and K-ras (N = 3). There were no significant differences between ras-negative and ras-positive patients according to age, sex, blood counts, cytogenetic abnormalities, or French-American-British classification. However, univariate analysis suggested a longer survival in ras-positive patients (P = .11). When adjusted for age, which was the most important factor affecting outcome, the presence of a ras mutation emerged as a significant predictor for improved survival (P = .03) and along with lower bone marrow blast counts (P = .02) and better cytogenetic category (P = .01). However, the presence of an aberrant ras allele was strongly correlated with lower bone marrow blast counts (P = .007). Thus, whether a mutation in the N-ras or K-ras proto-oncogenes directly affects treatment outcome or indirectly through an association with lower leukemic burden remains to be determined. Nevertheless, these findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

March 15, 1994

Volume

83

Issue

6

Start / End Page

1603 / 1611

Location

United States

Related Subject Headings

  • Survival Rate
  • Prognosis
  • Mutation
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Immunology
  • Humans
  • Genes, ras
  • Female
 

Citation

APA
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ICMJE
MLA
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Neubauer, A., Dodge, R. K., George, S. L., Davey, F. R., Silver, R. T., Schiffer, C. A., … Bloomfield, C. D. (1994). Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood, 83(6), 1603–1611.
Neubauer, A., R. K. Dodge, S. L. George, F. R. Davey, R. T. Silver, C. A. Schiffer, R. J. Mayer, E. D. Ball, D. Wurster-Hill, and C. D. Bloomfield. “Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia.Blood 83, no. 6 (March 15, 1994): 1603–11.
Neubauer A, Dodge RK, George SL, Davey FR, Silver RT, Schiffer CA, et al. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood. 1994 Mar 15;83(6):1603–11.
Neubauer, A., et al. “Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia.Blood, vol. 83, no. 6, Mar. 1994, pp. 1603–11.
Neubauer A, Dodge RK, George SL, Davey FR, Silver RT, Schiffer CA, Mayer RJ, Ball ED, Wurster-Hill D, Bloomfield CD. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood. 1994 Mar 15;83(6):1603–1611.

Published In

Blood

ISSN

0006-4971

Publication Date

March 15, 1994

Volume

83

Issue

6

Start / End Page

1603 / 1611

Location

United States

Related Subject Headings

  • Survival Rate
  • Prognosis
  • Mutation
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Immunology
  • Humans
  • Genes, ras
  • Female