Mutation position within evolutionary subclonal architecture in AML.

Abstract:

:Cytogenetic data suggest that acute myeloid leukemia (AML) develops through a process of branching evolution, especially during relapse and progression. Recent genomic data from AML cases using digital sequencing, temporal comparisons, xenograft cloning, and single-cell analysis indicate that most, if not all, AML cases emerge through branching evolution. According to a review of the current literature, the balanced translocations (t[15;17], t[8;21], and inv[16]) and nucleotide variants in DNMT3A and TET2 most commonly occur in the founding clone at diagnosis. These mutations are rarely gained or lost at relapse, and the latter 2 mutations are observed in elderly subjects with mosaic hematopoiesis antedating overt leukemia. In contrast, +8, +13, +22, -X, -Y, and nucleotide variants in FLT3, NRAS/KRAS, WT1, and KIT frequently occur in subclones and are observed either to emerge or to be lost at relapse. Because drugs that target mutations within a subclone are unlikely to eliminate all leukemic cells, it will be essential to understand not only which mutations a patient has but also how they organize within the leukemic subclonal architecture.

journal_name

Semin Hematol

journal_title

Seminars in hematology

authors

Welch JS

doi

10.1053/j.seminhematol.2014.08.004

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

273-81

issue

4

eissn

0037-1963

issn

1532-8686

pii

S0037-1963(14)00055-9

journal_volume

51

pub_type

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