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RAS mutations in pediatric leukemias with MLL gene rearrangements
N Mahgoub1, R I Parker, M R Hosler
1Department of Pediatrics, University of California, San Francisco, USA.
Genes, Chromosomes & Cancer
|April 2, 1998
Summary
RAS mutations are rare in infant leukemias with MLL gene translocations, primarily appearing in infant acute myeloid leukemia (AML) with MLL alterations. These findings suggest RAS mutations play a limited role in most pediatric leukemias involving MLL translocations.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Chromosomal translocations involving the MLL gene at 11q23 are common in infant de novo leukemia and chemotherapy-related leukemias.
- Leukemogenesis may require additional genetic events beyond MLL translocations.
Purpose of the Study:
- To investigate the frequency of KRAS and NRAS mutations in pediatric leukemias with MLL gene translocations.
- To determine the role of RAS mutations in different subtypes of pediatric leukemia with MLL alterations.
Main Methods:
- Analysis of 32 pediatric leukemia cases with MLL gene translocations.
- Utilized single-strand conformation polymorphism analysis and allele-specific restriction enzyme assays to detect KRAS and NRAS mutations.
Main Results:
- RAS mutations were found in 2 of 10 de novo acute myeloid leukemia (AML) cases, specifically in infant monoblastic variants.
- RAS mutations were absent in other subtypes, including acute lymphoblastic leukemia (ALL) and treatment-related leukemias with MLL translocations.
- This study reports the first co-occurrence of MLL gene translocation and RAS mutation in congenital leukemias.
Conclusions:
- RAS mutations are infrequent in pediatric leukemias with MLL gene translocations, with a notable presence in infant AML.
- RAS mutations appear to play a limited role in the pathogenesis of lymphoid and treatment-related leukemias characterized by MLL translocations.