Analysis of ras gene mutations in childhood myeloid leukaemia

Previous studies have shown that approximately 30% of adult acute myeloid leukaemias and 20% of adult acute lymphoid leukaemias contain point mutated ras oncogenes. In order to assess whether ras oncogenes are also involved in childhood leukaemias, we have used polymerase chain reaction (PCR) amplification and synthetic oligonucleotide probes to study the nature and frequency of ras gene mutations in childhood leukaemias, concentrating largely on the acute myeloid leukaemias (AML). Thirty‐four childhood presentation AML DNAs were screened for mutations in and around codons 12, 61 and 117 of N‐. K‐ and H‐ras. Eight of these samples (24%) contained ras mutations. As in the adult disease, the gene predominantly involved was N‐ras (6/8), with occasional activation of K‐ras (2/6). The most common base change was a G→A transition at codon 12 or 13 (4/8). Of the patients with mutant ras. 4/8 were diagnosed as AML FAB subtype M5. Five of the 34 childhood AMLs analysed displayed abnormalities of chromosome 7. However, none of these cases contained a mutant ras gene.

[1]  E. Liu,et al.  Mutations of the ras protooncogenes in chronic myelogenous leukemia: a high frequency of ras mutations in bcr/abl rearrangement-negative chronic myelogenous leukemia , 1989 .

[2]  Browett Pj,et al.  Analysis of ras gene mutations and methylation state in human leukemias. , 1989 .

[3]  Yunis Jj,et al.  Mechanisms of ras mutation in myelodysplastic syndrome. , 1989 .

[4]  W. Hiddemann,et al.  Acute myeloid leukemia: analysis of ras gene mutations and clonality defined by polymorphic X-linked loci. , 1989, Leukemia.

[5]  C. Marshall,et al.  RAS GENES AND ACUTE MYELOID LEUKAEMIA , 1989, British journal of haematology.

[6]  J. Bos,et al.  Mechanisms of ras mutation in myelodysplastic syndrome. , 1989, Oncogene.

[7]  J. Norton,et al.  Analysis of ras gene mutations and methylation state in human leukemias. , 1989, Oncogene.

[8]  E. Liu,et al.  Mutations of the ras protooncogenes in chronic myelogenous leukemia: a high frequency of ras mutations in bcr/abl rearrangement-negative chronic myelogenous leukemia. , 1989, Blood.

[9]  J. Jiricny,et al.  Relapse cell population differs from acute onset clone as shown by absence of the initially activated N-ras oncogene in a patient with acute myelomonocytic leukemia. , 1988, Blood.

[10]  F. McCormick,et al.  RAS mutations in myelodysplasia detected by amplification, oligonucleotide hybridization, and transformation. , 1988, Leukemia.

[11]  A. de la Chapelle,et al.  Clonal chromosomal abnormalities showing multiple-cell-lineage involvement in acute myeloid leukemia. , 1988, The New England journal of medicine.

[12]  J. Bos,et al.  The ras gene family and human carcinogenesis. , 1988, Mutation research.

[13]  R. Saiki,et al.  Analysis of RAS gene mutations in acute myeloid leukemia by polymerase chain reaction and oligonucleotide probes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Mullis,et al.  Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. , 1988, Science.

[15]  J. Adamson,et al.  Clonal development, stem-cell differentiation, and clinical remissions in acute nonlymphocytic leukemia. , 1987, The New England journal of medicine.

[16]  B. Franza,et al.  Expression of normal and mutant ras proteins in human acute leukemia. , 1987, Oncogene.

[17]  J. L. Bos,et al.  Mutations in N-ras predominate in acute myeloid leukemia. , 1987, Blood.

[18]  C. Marshall,et al.  ras gene activation in a minor proportion of the blast population in acute myeloid leukemia. , 1987, Oncogene.

[19]  M. Barbacid.  ras genes. , 1987, Annual review of biochemistry.

[20]  J. Griffin,et al.  Clonogenic cells in acute myeloblastic leukemia. , 1986, Blood.

[21]  G Flandrin,et al.  Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. , 1985, Annals of internal medicine.

[22]  C. Marshall,et al.  Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia , 1985, Nature.

[23]  J. Singer,et al.  A clonal complete remission in a patient with acute nonlymphocytic leukemia originating in a multipotent stem cell. , 1984, The New England journal of medicine.

[24]  C. Bloomfield,et al.  All patients with acute nonlymphocytic leukemia may have a chromosomal defect. , 1981, The New England journal of medicine.

[25]  J. Adamson,et al.  Acute nonlymphocytic leukemia: heterogeneity of stem cell origin. , 1981, Blood.

[26]  J. Adamson,et al.  Acute nonlymphocytic leukemia: heterogeneity of stem cell origin. , 1981, Blood.

[27]  J. Adamson,et al.  Acute nonlymphocytic leukemia: expression in cells restricted to granulocytic and monocytic differentiation. , 1979, The New England journal of medicine.

[28]  H. Moser,et al.  Partial deletion of long arm of chromosome 11[del(11)(q23)]: Jacobsen syndrome. Two new cases and review of the clinical findings. , 1977, Journal of medical genetics.

[29]  J. Rowley,et al.  Partial deletion of long arm of chromosome 17: a specific abnormality in acute promyelocytic leukemia? , 1976, Archives of internal medicine.