Genetic typing of CBL, ASXL1, RUNX1, TET2 and JAK2 in juvenile myelomonocytic leukaemia reveals a genetic profile distinct from chronic myelomonocytic leukaemia.
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.
Pérez
Benoîte
B
Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Robert Debré, Département de Génétique; Université Paris 7-Denis Diderot, Paris, France.
Kosmider
Olivier
O
Cassinat
Bruno
B
Renneville
Aline
A
Lachenaud
Julie
J
Kaltenbach
Sophie
S
Bertrand
Yves
Y
Baruchel
André
A
Chomienne
Christine
C
Fontenay
Michaela
M
Preudhomme
Claude
C
Cavé
Hélène
H
D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics*; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics*; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics
C473949:ASXL1 protein, human; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012097:Repressor Proteins