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FLT3 inhibition in acute myeloid leukaemia

Knapper, Steven 2007. FLT3 inhibition in acute myeloid leukaemia. British Journal of Haematology 138 (6) , pp. 687-699. 10.1111/j.1365-2141.2007.06700.x

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Abstract

FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that appears to play a significant role in leukaemogenesis. Activating mutations of FLT3 are present in approximately one-third of acute myeloid leukaemia patients and are associated with adverse clinical outcome, while many nonmutated cases also show evidence of FLT3 activation. FLT3 thus represents a potentially exciting molecular therapeutic target. A number of small-molecule tyrosine kinase inhibitors with anti-FLT3 activity have been developed and several of these compounds have entered early phase clinical trials where clinical anti-leukaemic activity has been demonstrated. The depth and duration of clinical responses to FLT3 inhibitor monotherapy have been modest, however, and a number of mechanisms by which blasts may acquire resistance have been proposed. Based on preclinical evidence of synergy with conventional chemotherapy, several combination trials are now underway. FLT3 inhibition may also be effective used in combination with other molecularly targeted agents, in postchemotherapy stem-cell-directed maintenance therapy and in MLL-rearranged infant acute lymphoblastic leukaemia.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Wiley-Blackwell
ISSN: 0007-1048
Date of First Compliant Deposit: 26 September 2017
Last Modified: 11 Oct 2017 04:57
URI: http://orca.cf.ac.uk/id/eprint/105011

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