Matches in SemOpenAlex for { <https://semopenalex.org/work/W1996307710> ?p ?o ?g. }
- W1996307710 endingPage "268" @default.
- W1996307710 startingPage "260" @default.
- W1996307710 abstract "Internal tandem duplication (ITD) of the fms-like tyrosine kinase 3 (FLT3) gene is a gain-of-function mutation common in acute myeloid leukaemia (AML). It is associated with inferior prognosis and response to chemotherapy. Single base mutations at the FLT3 tyrosine kinase domain (TKD) also leads to a gain of function, although its prognostic significance is less well defined because of its rarity. The clinical benefits of FLT3 inhibition are generally limited to AML with FLT3-ITD. However, responses are transient and leukaemia progression invariably occurs. There is compelling evidence that leukaemia clones carrying both ITD and TKD mutations appear when resistance to FLT3 inhibitors occurs. Interestingly, the emergence of double ITD and TKD mutants can be recapitulated in vitro when FLT3-ITD+ leukaemia cell lines are treated with mutagens and FLT3 inhibitors. Furthermore, murine xenotransplantation models also suggest that, in some cases, the FTL3-ITD and TKD double mutants actually exist in minute amounts before treatment with FLT3 inhibitors, expand under the selection pressure of FLT3 inhibition and become the predominant resistant clone(s) during the drug-refractory phase. On the basis of this model of clonal evolution, a multipronged strategy using more potent FLT3 inhibitors, and a combinatorial approach targeting both FLT3-dependent and FLT3-independent pathways, will be needed to improve outcome." @default.
- W1996307710 created "2016-06-24" @default.
- W1996307710 creator A5016952242 @default.
- W1996307710 creator A5017722432 @default.
- W1996307710 creator A5039769794 @default.
- W1996307710 date "2012-07-16" @default.
- W1996307710 modified "2023-10-17" @default.
- W1996307710 title "FLT3 inhibition: a moving and evolving target in acute myeloid leukaemia" @default.
- W1996307710 cites W1965554041 @default.
- W1996307710 cites W1967269645 @default.
- W1996307710 cites W1969317010 @default.
- W1996307710 cites W1969775814 @default.
- W1996307710 cites W1970039100 @default.
- W1996307710 cites W1971028883 @default.
- W1996307710 cites W1971625992 @default.
- W1996307710 cites W1974674483 @default.
- W1996307710 cites W1975137294 @default.
- W1996307710 cites W1976770929 @default.
- W1996307710 cites W1977902316 @default.
- W1996307710 cites W1978544029 @default.
- W1996307710 cites W1980904297 @default.
- W1996307710 cites W1981811959 @default.
- W1996307710 cites W1984209370 @default.
- W1996307710 cites W1985877500 @default.
- W1996307710 cites W1986505614 @default.
- W1996307710 cites W1988062934 @default.
- W1996307710 cites W1988356885 @default.
- W1996307710 cites W1989704333 @default.
- W1996307710 cites W1990030298 @default.
- W1996307710 cites W1990870968 @default.
- W1996307710 cites W1990924336 @default.
- W1996307710 cites W1990992718 @default.
- W1996307710 cites W1993300766 @default.
- W1996307710 cites W1994724349 @default.
- W1996307710 cites W1999356404 @default.
- W1996307710 cites W2000273667 @default.
- W1996307710 cites W2002927399 @default.
- W1996307710 cites W2002962363 @default.
- W1996307710 cites W2003067220 @default.
- W1996307710 cites W2004304358 @default.
- W1996307710 cites W2005726155 @default.
- W1996307710 cites W2009816863 @default.
- W1996307710 cites W2010510798 @default.
- W1996307710 cites W2011853681 @default.
- W1996307710 cites W2016883830 @default.
- W1996307710 cites W2017107901 @default.
- W1996307710 cites W2020481917 @default.
- W1996307710 cites W2021425093 @default.
- W1996307710 cites W2021619817 @default.
- W1996307710 cites W2022330354 @default.
- W1996307710 cites W2023560061 @default.
- W1996307710 cites W2024072740 @default.
- W1996307710 cites W2024162263 @default.
- W1996307710 cites W2026970599 @default.
- W1996307710 cites W2030294618 @default.
- W1996307710 cites W2033025320 @default.
- W1996307710 cites W2034820298 @default.
- W1996307710 cites W2036716522 @default.
- W1996307710 cites W2040322688 @default.
- W1996307710 cites W2041027929 @default.
- W1996307710 cites W2041840612 @default.
- W1996307710 cites W2042382807 @default.
- W1996307710 cites W2045166052 @default.
- W1996307710 cites W2047406713 @default.
- W1996307710 cites W2050022454 @default.
- W1996307710 cites W2050338667 @default.
- W1996307710 cites W2050768356 @default.
- W1996307710 cites W2051763439 @default.
- W1996307710 cites W2052386066 @default.
- W1996307710 cites W2052515415 @default.
- W1996307710 cites W2056465113 @default.
- W1996307710 cites W2057335049 @default.
- W1996307710 cites W2057676487 @default.
- W1996307710 cites W2059150276 @default.
- W1996307710 cites W2060794068 @default.
- W1996307710 cites W2062115635 @default.
- W1996307710 cites W2063526201 @default.
- W1996307710 cites W2063972153 @default.
- W1996307710 cites W2063981273 @default.
- W1996307710 cites W2064051300 @default.
- W1996307710 cites W2064260864 @default.
- W1996307710 cites W2065831993 @default.
- W1996307710 cites W2069931679 @default.
- W1996307710 cites W2071432029 @default.
- W1996307710 cites W2075439952 @default.
- W1996307710 cites W2080949102 @default.
- W1996307710 cites W2083500049 @default.
- W1996307710 cites W2086039105 @default.
- W1996307710 cites W2089363671 @default.
- W1996307710 cites W2093144236 @default.
- W1996307710 cites W2101651820 @default.
- W1996307710 cites W2102185636 @default.
- W1996307710 cites W2104983860 @default.
- W1996307710 cites W2105214030 @default.
- W1996307710 cites W2109869665 @default.
- W1996307710 cites W2110648386 @default.
- W1996307710 cites W2111210736 @default.
- W1996307710 cites W2113230030 @default.