Clonal dynamics in a case of acute monoblastic leukemia that later developed myeloproliferative neoplasm View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-02-07

AUTHORS

Shinya Sato, Hidehiro Itonaga, Masataka Taguchi, Yasushi Sawayama, Daisuke Imanishi, Hideki Tsushima, Tomoko Hata, Yukiyoshi Moriuchi, Hiroyuki Mishima, Akira Kinoshita, Koh-ichiro Yoshiura, Yasushi Miyazaki

ABSTRACT

In acute myeloid leukemia (AML), patients may harbor pre-leukemic hematopoietic stem cells (HSCs) containing some, but not all, of the mutations observed in the leukemic cells. These pre-leukemic HSCs may survive induction chemotherapy and contribute to AML relapse by obtaining additional mutations. We report here an acute monoblastic leukemia (AMoL) patient who later developed an unclassifiable myeloproliferative neoplasm (MPN-U). Whole-exome sequencing and cluster analysis demonstrated the presence of three distinct major clones during the clinical course: (1) an AMoL clone with ASXL1, CBL, and NPM1 somatic mutations, likely associated with the pathogenesis, and GATA2, SRSF2, and TET2 mutations, (2) an AMoL remission clone, with mutated GATA2, SRSF2, and TET2 only (possibly the founding clone (pre-leukemic HSC) that survived chemotherapy), (3) a small subclone which had JAK2 mutation during the AMoL remission, appearing at MPN-U manifestation with additional mutations. These findings suggest that pre-leukemic HSCs in AML patients may give rise to non-AML myeloid malignancies. This is the first report to analyze the clonal evolution from AMoL to MPN-U, which may provide new insight into the development of myeloid malignancies. More... »

PAGES

213-217

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-018-2419-1

DOI

http://dx.doi.org/10.1007/s12185-018-2419-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100859804

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29417354


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61 findings
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63 hematopoietic stem cells
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65 insights
66 leukemia
67 leukemia patients
68 leukemic cells
69 major clones
70 malignancy
71 manifestations
72 monoblastic leukemia
73 mutations
74 myeloid leukemia
75 myeloid malignancies
76 myeloproliferative neoplasms
77 neoplasms
78 new insights
79 pathogenesis
80 patients
81 pre-leukemic hematopoietic stem cells
82 presence
83 relapse
84 remission
85 report
86 sequencing
87 small subclones
88 somatic mutations
89 stem cells
90 subclones
91 unclassifiable myeloproliferative neoplasm
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