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Serum Flt3 ligand is a biomarker of progenitor cell mass and prognosis in acute myeloid leukemia

Lookup NU author(s): Dr Paul Milne, Dr Venetia Bigley, Dr Amy Publicover, Sarah Pagan, Dr Helen Marr, Dr Gail Jones, Professor Anne Dickinson, Professor Matthew Collin

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Abstract

© 2019 by The American Society of HematologyFms-like tyrosine kinase 3 (Flt3) is expressed on progenitor cells and acute myeloid leukemia (AML) blasts. Fms-like tyrosine kinase 3 ligand (Flt3L) is detectable during homeostasis and increases in hypoplasia due to genetic defects or treatment with cytoreductive agents. Conversely, Flt31 AML is associated with depletion of Flt3L to undetectable levels. After induction chemotherapy, Flt3L is restored in patients entering complete remission (CR) but remains depressed in those with refractory disease. Weekly sampling reveals marked differences in the kinetics of Flt3L response during the first 6 weeks of treatment, proportionate to the clearance of blasts and cellularity of the bone marrow. In the UK NCRI AML17 trial, Flt3L was measured at day 26 in a subgroup of 140 patients with Flt3 mutation randomized to the tyrosine kinase inhibitor lestaurtinib or placebo. In these patients, attainment of CR was associated with higher Flt3L at day 26 (Mann-Whitney U P, .0001). Day 26 Flt3L was also associated with survival; Flt3L #291 pg/mL was associated with inferior event-free survival (EFS), and Flt3L .1185 pg/mL was associated with higher overall survival (OS; P 5 .0119). The separation of EFS and OS curves increased when minimal residual disease (MRD) status was combined with Flt3L measurement, and Flt3L retained a near-significant association with survival after adjusting for MRD in a proportional hazards model. Serial measurement of Flt3L in patients who had received a hematopoietic stem cell transplant for AML illustrates the potential value of monitoring Flt3L to identify relapse. Measurement of Flt3L is a noninvasive test with the potential to inform clinical decisions in patients with AML.


Publication metadata

Author(s): Milne P, Wilhelm-Benartzi C, Grunwald MR, Bigley V, Dillon R, Freeman SD, Gallagher K, Publicover A, Pagan S, Marr H, Jones GL, Dickinson AM, Grech A, Burnett AK, Russell NH, Levis M, Knapper S, Collin M

Publication type: Article

Publication status: Published

Journal: Blood Advances

Year: 2019

Volume: 3

Issue: 20

Pages: 3052-3061

Online publication date: 22/10/2019

Acceptance date: 30/07/2019

ISSN (print): 2473-9529

ISSN (electronic): 2473-9537

Publisher: American Society of Hematology

URL: https://doi.org/10.1182/bloodadvances.2019000197

DOI: 10.1182/bloodadvances.2019000197

PubMed id: 31648336


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