Genetic typing of CBL, ASXL1, RUNX1, TET2 and JAK2 in juvenile myelomonocytic leukaemia reveals a genetic profile distinct from chronic myelomonocytic leukaemia
Open Access
- 19 October 2010
- journal article
- Published by Wiley in British Journal of Haematology
- Vol. 151 (5), 460-468
- https://doi.org/10.1111/j.1365-2141.2010.08393.x
Abstract
JMML and CMML are rare myelodysplastic/myeloproliferative neoplasms occurring at both ends of life. To investigate relationships between JMML and CMML, genes recently involved in CMML were studied in 68 JMML patients. Mutations in TET2, RUNX1 and JAK2V617F are involved in myelodysplastic and/or myeloproliferative syndromes, and more specifically in CMML but were not found in JMML. Pangenomic analysis by SNP‐array showed no abnormality at these loci. Three frameshift mutations of ASXL1 leading to a truncated protein were found in three patients (4%) with late onset JMML displaying also RAS activating mutations. Homozygous mutations of CBL with 11q loss of heterozygosity were found in five (7%) JMML. CBL substitutions were different from those reported in CMML, exclusive from other RAS activating mutations, and were germline in all patients. Overall, the pattern of genetic lesions observed in JMML differed from that of CMML. Although signalling deregulation is involved in CMML, transcriptional deregulation seems to play a pivotal role, with mutation of RUNX1, ASXL1 or TET2. Conversely, none of these genes involved in transcription or chromatin remodelling was found to be significantly altered in JMML, while CBL mutations confirm the central role of RAS and growth factor signalling deregulation in JMML.Keywords
This publication has 50 references indexed in Scilit:
- High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progressionLeukemia, 2010
- Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemiaLeukemia, 2010
- Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemiasLeukemia, 2009
- Mutations of ASXL1 gene in myeloproliferative neoplasmsLeukemia, 2009
- Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignanciesBlood, 2009
- Mutation inTET2in Myeloid CancersNew England Journal of Medicine, 2009
- 250K Single Nucleotide Polymorphism Array Karyotyping Identifies Acquired Uniparental Disomy and Homozygous Mutations, Including Novel Missense Substitutions of c-Cbl, in Myeloid MalignanciesCancer Research, 2008
- Juvenile myelomonocytic leukemia: A report from the 2nd International JMML SymposiumLeukemia Research, 2008
- Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemiaLeukemia, 2008
- Subacute and chronic myelomonocytic leukemia in children (juvenile CML). Clinical and hematologic observations, and identification of prognostic factorsCancer, 1984