Clonal dynamics in a case of acute monoblastic leukemia that later developed myeloproliferative neoplasm
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....
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Published in | International journal of hematology Vol. 108; no. 2; pp. 213 - 217 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Tokyo
Springer Japan
01.08.2018
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 |
ISSN: | 0925-5710 1865-3774 |
DOI: | 10.1007/s12185-018-2419-1 |