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Lineage‐dependent skewing of loss of heterozygosity ( LOH ) of KRAS gene in a case of juvenile myelomonocytic leukemia
Author(s) -
Tokuda Kiriko,
EguchiIshimae Minenori,
Iwabuki Hidehiko,
Kawakami Sanae,
Tauchi Hisamichi,
Ishii Eiichi,
Eguchi Mariko
Publication year - 2015
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12355
Subject(s) - juvenile myelomonocytic leukemia , loss of heterozygosity , kras , biology , haematopoiesis , lineage (genetic) , cancer research , leukemia , mutation , stem cell , progenitor cell , allele , immunology , genetics , gene
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 − CD 34 + CD 38 − 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.

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