Document Type

Article

Publication Date

1-1-2017

Identifier

PMCID: PMC5177472 DOI: 10.1111/bjh.14413

Abstract

Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in paediatric and adult AML.

Journal Title

British journal of haematology

Volume

176

Issue

1

First Page

86

Last Page

91

MeSH Keywords

Adolescent; Adult; Aged; Aged, 80 and over; Carrier Proteins; Cell Adhesion Molecules, Neuronal; Child; Child, Preschool; Drug Resistance, Neoplasm; Extracellular Matrix Proteins; Female; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genomics; Humans; Infant; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Nerve Tissue Proteins; Nuclear Proteins; Pregnancy; Remission Induction; Repressor Proteins; Serine Endopeptidases; Treatment Failure; Young Adult

Keywords

cytogenetically normal acute myeloid leukaemia; induction failure; paediatric leukaemia; primary chemoresistance; targeted deep sequencing genomics; AML; children; babies; teenagers

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