Acquired isodisomy on chromosome 13 at diagnosis results in impaired overall survival in patients with FLT3-ITD mutant acute myeloid leukaemia
Loke, J. C. T. Akiki, S. Borrow, J. Ewing, J. Bokhari, S. W. Chandra, D. Arrazi, J. Hazlewood, P. Arthur, K. Walsh, J.
Loke, J. C. T.
Akiki, S.
Borrow, J.
Ewing, J.
Bokhari, S. W.
Chandra, D.
Arrazi, J.
Hazlewood, P.
Arthur, K.
Walsh, J.
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Affiliation
University Hospitals Birmingham NHS Foundation Trust; West Midlands Regional Genetics Laboratory, Birmingham; University Hospitals Coventry and Warwickshire NHS Trust; University Hospital of North Staffordshire; Worcestershire Royal Hospital; New Cross Hospital, Wolverhampton; Sandwell and West Birmingham Hospitals NHS Trust; The Dudley Group NHS Foundation Trust; South Warwickshire University NHS Foundation Trust; University of Birmingham
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Publication date
2015-06-19
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Abstract
Internal tandem duplication (ITD) mutations in the FLT3 gene on chromosome 13 occur in 25% of patients with acute myeloid leukaemia (AML) and result in impaired overall survival (OS). Patients with a high allelic ratio (AR) of ITD mutant to wild-type FLT3 in genomic DNA have an even poorer prognosis. AR may be a predictor of response to FLT3 inhibitors and may also interact with other mutations in influencing disease risk.
AR may be dependent on a number of factors including loss of the wild-type allele. Acquired isodisomy (AID) results in loss of the wild-type allele, through duplication of the mutant allele with segmental loss of the wild-type allele. Although studies have shown the importance of AID at chromosome 13 (AID13) at relapse, the impact of AID13 at diagnosis is unclear. The study reported in this Letter to the Editor aimed to identify the relationship between AID13 and FLT3-ITD AR and investigated the outcomes of patients with AID13.
Citation
Loke JC, Akiki S, Borrow J, Ewing J, Bokhari SW, Chandra D, Arrazi J, Hazlewood P, Arthur K, Walsh J, Membwange Y, Wandroo FA, Watts A, Borg A, Brock K, Ferguson P, Craddock C, Griffiths M, Raghavan M. Acquired isodisomy on chromosome 13 at diagnosis results in impaired overall survival in patients with FLT3-ITD mutant acute myeloid leukaemia. Leukemia. 2015 Dec;29(12):2404-7. doi: 10.1038/leu.2015.148. Epub 2015 Jun 19.
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Correspondence