Lineage-dependent skewing of loss of heterozygosity (LOH) of KRAS gene in a case of juvenile myelomonocytic leukemia.
Juvenile myelomonocytic leukemia (JMML) is a clonal disease arising from abnormal hematopoietic stem cells, although the involvement of lymphoid lineage differs among reported cases. Here, we present a case of JMML with a KRAS G13D mutation. The mutation was detected in various hematopoietic lineages, including T and B lymphocytes and also in lineage(-) CD34(+) CD38(-) hematopoietic stem cells, showing a different percentage of affected cells in each lineage. Single cell-based analysis of hematopoietic cells revealed the loss of wild-type KRAS in a significant proportion of G13D-harboring cells. The percentage of loss of heterozygosity (LOH)/non-LOH cells showed lineage-dependent skewing in hematopoietic cells. The loss of the wild-type KRAS allele may be a common secondary genetic change in KRAS-related JMML and may affect the differentiation behavior of early JMML progenitors.
Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan.
Kiriko
K
Tokuda
Minenori
M
Eguchi-Ishimae
Hidehiko
H
Iwabuki
Sanae
S
Kawakami
Hisamichi
H
Tauchi
Eiichi
E
Ishii
Mariko
M
Eguchi
D000483:Alleles; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D054429:Leukemia, Myelomonocytic, Juvenile / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
KRAS; juvenile myelomonocytic leukemia; loss of heterozygosity