title: K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements.
abstract: BACKGROUND
  It is believed that Ras mutations drive the proliferation of leukemic cells. The objective of this study was to investigate the association of Ras mutations with childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) with special reference to the presence or absence of mixed-lineage leukemia gene (MLL) rearrangements.
  
  
  METHODS
  Bone marrow samples from 313 children with B-precursor ALL and 130 children with de novo AML were studied at diagnosis. Southern blot analysis was used to detect MLL rearrangements, and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was used to detect common MLL fusion transcripts. Complementary DNA panhandle PCR was used to identify the infrequent or unknown MLL partner genes. DNA PCR or RT-PCR followed by direct sequencing was performed to detect mutations at codons 12, 13, and 61 of the N-Ras and K-Ras genes.
  
  
  RESULTS
  Twenty of 313 patients with B-precursor ALL and 17 of 130 patients with de novo AML had MLL rearrangements. N-Ras mutations were detected in 2 of 20 patients with MLL-positive ALL and in 27 of 293 patients with MLL-negative ALL (P = 1.000). N-Ras mutations were detected in 2 of 17 patients with MLL-positive AML and in 14 of 113 patients with MLL-negative AML (P = 1.000). K-Ras mutations were present in 8 of 20 patients with MLL-positive ALL compared with 32 of 293 patients with MLL-negative ALL (P = 0.001). K-Ras mutations were detected in 3 of 17 patients with MLL-positive AML compared with 5 of 113 patients with MLL-negative AML (P = 0.069).
  
  
  CONCLUSIONS
  Ras mutations were detected in 20.8% of patients with childhood B-precursor ALL and in 17.7% of patients with childhood AML. MLL-positive B-precursor ALL was associated closely with Ras mutations (50%), especially with K-Ras mutations (40%), whereas MLL-positive AML was not associated with Ras mutations.
authors.affiliation: Division of Pediatric Hematology-Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Liang
authors.forename: Lee-Yung
authors.initials: LY
authors.lastname: Shih
authors.forename: Jen-Fen
authors.initials: JF
authors.lastname: Fu
authors.forename: Huei-Ying
authors.initials: HY
authors.lastname: Li
authors.forename: Hsiu-I
authors.initials: HI
authors.lastname: Wang
authors.forename: Iou-Jih
authors.initials: IJ
authors.lastname: Hung
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Yang
authors.forename: Tang-Her
authors.initials: TH
authors.lastname: Jaing
authors.forename: Shu-Huey
authors.initials: SH
authors.lastname: Chen
authors.forename: Hsi-Che
authors.initials: HC
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D015321:Gene Rearrangement; D011905:Genes, ras; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction