FLT3-ITD allelic ratio and HLF expression predict FLT3 inhibitor efficacy in adult AML

Kivioja, J (author)

Malani, D (author)

Kumar, A (author)

Kontro, M (author)

Parsons, A (author)

Heckman, CA (author)

(creator_code:org_t)

2021-12-07
2021
English.
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 23565-

Related links:: https://www.nature.c...; show more...; http://kipublication...; https://doi.org/10.1...; show less...

Abstract Subject headings

FLT3 internal tandem duplication (FLT3-ITD) is a frequent mutation in acute myeloid leukemia (AML) and remains a strong prognostic factor due to high rate of disease recurrence. Several FLT3-targeted agents have been developed, but determinants of variable responses to these agents remain understudied. Here, we investigated the role FLT3-ITD allelic ratio (ITD-AR), ITD length, and associated gene expression signatures on FLT3 inhibitor response in adult AML. We performed fragment analysis, ex vivo drug testing, and next generation sequencing (RNA, exome) to 119 samples from 87 AML patients and 13 healthy bone marrow controls. We found that ex vivo response to FLT3 inhibitors is significantly associated with ITD-AR, but not with ITD length. Interestingly, we found that the HLF gene is overexpressed in FLT3-ITD+ AML and associated with ITD-AR. The retrospective analysis of AML patients treated with FLT3 inhibitor sorafenib showed that patients with high HLF expression and ITD-AR had better clinical response to therapy compared to those with low ITD-AR and HLF expression. Thus, our findings suggest that FLT3 ITD-AR together with increased HLF expression play a role in variable FLT3 inhibitor responses observed in FLT3-ITD+ AML patients.

By the author/editor: Kivioja, J; Malani, D; Kumar, A; Kontro, M; Parsons, A; Kallioniemi, O; show more...; Heckman, CA; show less...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.