Lineage‐dependent skewing of loss of heterozygosity (LOH) of KRAS gene in a case of juvenile myelomonocytic leukemia

• Published in: European journal of haematology 2015-02, Vol.94 (2), p.177-181
• Main Authors: Tokuda, Kiriko, Eguchi‐Ishimae, Minenori, Iwabuki, Hidehiko, Kawakami, Sanae, Tauchi, Hisamichi, Ishii, Eiichi, Eguchi, Mariko
• Format: Article
• Language: English
• Subjects: Alleles; Bone Marrow - pathology; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; Cell Lineage - genetics; Humans; Immunophenotyping; Infant; juvenile myelomonocytic leukemia; KRAS; Leukemia, Myelomonocytic, Juvenile - diagnosis; Leukemia, Myelomonocytic, Juvenile - genetics; Leukemia, Myelomonocytic, Juvenile - metabolism; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Loss of Heterozygosity; Male; Mutation; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.12355

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.