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Genetic typing of CBL , ASXL1 , RUNX1 , TET2 and JAK2 in juvenile myelomonocytic leukaemia reveals a genetic profile distinct from chronic myelomonocytic leukaemia
Author(s) -
Pérez Benoîte,
Kosmider Olivier,
Cassinat Bruno,
Renneville Aline,
Lachenaud Julie,
Kaltenbach Sophie,
Bertrand Yves,
Baruchel André,
Chomienne Christine,
Fontenay Michaela,
Preudhomme Claude,
Cavé Hélène
Publication year - 2010
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2010.08393.x
Subject(s) - juvenile myelomonocytic leukemia , frameshift mutation , biology , cancer research , germline , chronic myelomonocytic leukemia , germline mutation , loss of heterozygosity , genetics , mutation , neuroblastoma ras viral oncogene homolog , runx1 , myelodysplastic syndromes , gene , transcription factor , immunology , kras , haematopoiesis , stem cell , bone marrow , allele
Summary 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 JAK2 V617F 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.