This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
RAS mutations and clonality analysis in children with juvenile myelomonocytic
leukemia (JMML)
Flotho C, Valcamonica S, Mach-Pascual S, Schmahl G, Corral L, Ritterbach J, Hasle H, Aricò M, Biondi A, Niemeyer CM.
Children's Hospital, University of Freiburg, Germany.
Juvenile myelomonocytic leukemia (JMML) is a severe and rare form of leukemia affecting young children. When this article was written in 1999, the disease was also known as 'juvenile chronic myelogenous leukemia' (JCML) or 'chronic myelomonocyic leukemia in childhood' (CMML). Currently it is known only as JMML (CMML is known as a separate but related form of leukemia). From previous studies, the authors of this study knew that the division of blood cells is abnormal in patients with JMML. They also know that the cells are hypersensitive to GM-CSF (Granulocyte-macrophage colony-stimulating factor), which is a protein secreted by white blood cells and several other cell types. GM-CSF is known to interact with proteins coded by the RAS genes, the aim of the study was to observe whether the patients of JMML have mutations in these genes. The researchers focused on the mutations that affect how the RAS proteins communicate with each other, as it is thought that the miscommunication of signals between cells results in aberrant blood cell division.
The results of the study indicate that there are point mutations in the 12, 13 or 61 codons of the RAS genes that were detected in 18% of the children with JMML. Two of the children had a mutation in codon 12 of the NRAS gene, three children in codon 13 of NRAS, while one child had a mutation in codon 13 of KRAS. The researchers concluded that about 20% of JMML patients have RAS mutations without NF1 (Neurofibromatosis type I, a human genetic disorder that is also associated with JMML). The researchers speculate that there could be some other abnormalities in the RAS signaling pathway that is yet to be defined that causes JMML.
Children's Hospital, University of Freiburg, Germany.
Juvenile myelomonocytic leukemia (JMML) is a severe and rare form of leukemia affecting young children. When this article was written in 1999, the disease was also known as 'juvenile chronic myelogenous leukemia' (JCML) or 'chronic myelomonocyic leukemia in childhood' (CMML). Currently it is known only as JMML (CMML is known as a separate but related form of leukemia). From previous studies, the authors of this study knew that the division of blood cells is abnormal in patients with JMML. They also know that the cells are hypersensitive to GM-CSF (Granulocyte-macrophage colony-stimulating factor), which is a protein secreted by white blood cells and several other cell types. GM-CSF is known to interact with proteins coded by the RAS genes, the aim of the study was to observe whether the patients of JMML have mutations in these genes. The researchers focused on the mutations that affect how the RAS proteins communicate with each other, as it is thought that the miscommunication of signals between cells results in aberrant blood cell division.
The results of the study indicate that there are point mutations in the 12, 13 or 61 codons of the RAS genes that were detected in 18% of the children with JMML. Two of the children had a mutation in codon 12 of the NRAS gene, three children in codon 13 of NRAS, while one child had a mutation in codon 13 of KRAS. The researchers concluded that about 20% of JMML patients have RAS mutations without NF1 (Neurofibromatosis type I, a human genetic disorder that is also associated with JMML). The researchers speculate that there could be some other abnormalities in the RAS signaling pathway that is yet to be defined that causes JMML.
| rasnjmml.pdf |
References
1) RAS mutations and clonality analysis in children with juvenile myelomonocytic
leukemia (JMML)
http://www.ncbi.nlm.nih.gov/pubmed/10049057
leukemia (JMML)
http://www.ncbi.nlm.nih.gov/pubmed/10049057
