K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements.
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.
Liang
Der-Cherng
DC
Division of Pediatric Hematology-Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
Shih
Lee-Yung
LY
Fu
Jen-Fen
JF
Li
Huei-Ying
HY
Wang
Hsiu-I
HI
Hung
Iou-Jih
IJ
Yang
Chao-Ping
CP
Jaing
Tang-Her
TH
Chen
Shu-Huey
SH
Liu
Hsi-Che
HC
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