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Comprehensive genetic analysis of donor cell derived leukemia with KMT2A rearrangement
Author(s) -
Taniguchi Rieko,
Muramatsu Hideki,
Okuno Yusuke,
Suzuki Kyogo,
Obu Satoshi,
Nakatochi Masahiro,
Shimamura Teppei,
Takahashi Yoshiyuki,
Horikoshi Yasuo,
Watanabe Kenichiro,
Kojima Seiji
Publication year - 2018
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.26823
Subject(s) - medicine , leukemia , exome sequencing , germline mutation , acute leukemia , cancer research , genetic predisposition , germline , bone marrow , transplantation , mutation , immunology , genetics , pathology , gene , biology , disease
Abstract Background Donor cell leukemia (DCL) occurs after allogeneic hematopoietic stem cell transplantation. Several mechanisms, including occult leukemic/preleukemic subclones in the donor graft and germline predisposition to leukemia, are proposed to be associated with DCL's molecular pathogenesis. We report a comprehensive genetic analysis of a patient with KMT2A ‐rearranged DCL after allogeneic bone marrow transplantation for refractory cytopenia of childhood. Procedure We performed a whole‐exome sequencing of the recipient's peripheral blood before transplant and the donor's peripheral blood and the recipient's bone marrow at the time of DCL diagnosis. RNA sequencing was also performed to detect fusion genes in DCL blasts. Results There were no germline mutations that were associated with a predisposition to leukemia in the recipient and donor. Furthermore, there were no detectable somatic alterations except KMT2A ‐ MLLT10 and other related gene fusions in DCL. KMT2A ‐ MLLT10 was not detectable in the donor's bone marrow. Conclusion We propose a novel pattern of the molecular pathogenesis of DCL solely involving a genetic mutation acquired after transplant with no identifiable genetic factor related to the donor and recipient.