K‐ras mutations and N‐ras mutations in childhood acute leukemias with or without mixed‐lineage leukemia gene rearrangements

• Published in: Cancer Vol. 106; no. 4; pp. 950 - 956
• Main Authors: Liang, Der‐Cherng, Shih, Lee‐Yung, Fu, Jen‐Fen, Li, Huei‐Ying, Wang, Hsiu‐I, Hung, Iou‐Jih, Yang, Chao‐Ping, Jaing, Tang‐Her, Chen, Shu‐Huey, Liu, Hsi‐Che
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.02.2006; Wiley-Liss
• Subjects: Acute Disease; Adolescent; Biological and medical sciences; Blotting, Southern; Child; Child, Preschool; childhood acute lymphoblastic leukemia; childhood acute myeloid leukemia; DNA Mutational Analysis; Female; Gene Rearrangement; Genes, ras; Hematologic and hematopoietic diseases; Humans; Infant; K‐Ras mutations; Leukemia, Myeloid - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; MLL rearrangements; N‐Ras mutations; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Reverse Transcriptase Polymerase Chain Reaction; Tumors; Human; n ras Gene; childhood acute lymphoblastic leukemia; Acute; Acute leukemia; Malignant hemopathy; N-Ras mutations; childhood acute myeloid leukemia; K ras Gene; Cancerology; Lymphoproliferative syndrome; C-Onc gene; Gene rearrangement; Mixed lineage; MLL rearrangements; Acute lymphocytic leukemia; Mutation; Onc gene; Ras gene; K-Ras mutations; Child; Protooncogene; Acute myelocytic leukemia
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21687

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. Cancer 2006. © 2006 American Cancer Society. In a large‐scale study using direct sequencing for each polymerase chain reaction product, the authors documented the frequency of K‐Ras and N‐Ras mutations in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia. K‐Ras mutations were detected in 40% of patients who had ALL that was positive for mixed‐lineage leukemia gene (MLL) rearrangements, a proportion that was significantly higher compared with that among patients who had MLL‐negative B‐precursor ALL.