Moreover, we performed an analysis of the correlation of FLT3-ITD length and insertion sites with the mutational landscape of AML, which has not been carried out thus far. In the frontline setting (n=4), the CRc rate with the triplet was 100% with FLT3-PCR negativity in all four patients56. An analysis of OS censoring at the time of allo-HSCT did not yield significant results (data not shown). Nature 485, 260263 (2012). Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 gene ( FLT3) confer a poor prognosis in adult AML. CAS Schlenk, R. F. et al. Conceptualization, T.C., J.M.A., E.B. PubMed J. Hematol. Patterns of resistance differ in patients with acute myeloid leukemia treated with type I versus type II FLT3-inhibitors. and P.M.; Validation, T.C., J.M.A., E.B. Blood 124, 34413449 (2014). Go to: Introduction The survival rates in patients 60 years of age were also similar across NPM1 mut /FLT3 wt, NPM1 mut /FLT3-ITD low, and NPM1 mut . FLT3 plays a role in cell survival, proliferation and differentiation of hematopoietic progenitor cells. "For patients with AML, the 5-year survival rate is only about 29%," said Dr. Erba. CR or CRi was achieved in 70% of the patients in both groups (P=0.9). In patients with relapsed or refractory FLT3mut AML (Fig. TM,transmembrane domain; JMD, juxtamembrane domain; JMD-B, binding motif; JMD-S, switch motif; JMD-Z, zipper motif; HR, hinge region; TKD1, tyrosine kinase domain 1; B1, beta1-sheet; NBL, nucleotide binding loop; B2, beta2-sheet; and TKD2, tyrosine kinase domain 2. ISSN 2045-2322 (online). However, emerging data does suggest that patients with FLT3-ITDmut AR<0.5 and NPM1 co-mutation without concurrent high-risk mutations such as DNMT3A, TP53, TET2, or high-risk cytogenetics may be a more favorable subset, who may be considered for induction, consolidation followed by maintenance therapy without ASCT on a case by case basis if they achieve early MRD negativity using a highly sensitive MRD assay. Favorable relapse risk and OS were seen in NPM1mut with FLT3 wild-type; intermediate prognosis in FLT3-ITDmut with concurrent NPM1mut, and adverse prognosis in FLT3-ITDmut with NPM1 wild-type patients16. Upregulation of Bcl-2 confers resistance to FLT3 inhibition in FLT3-ITD AML with secondary acquired mutations. However, in a recently released planned interim analysis, the study did not meet its primary endpoint of overall survival and may be terminated for futility46. Larger studies of ITD size, although they did not employ these cutoffs, did not find prognostic power of this measure, which corroborates our results. 93, 11361141 (2018). This study shows that the size of FLT3-ITD mutations has no prognostic impact in terms of survival, relapse or CR rate among newly diagnosed AML patients treated with first-line intensive regimens. This work is submitted in partial fulfillment of the requirement for the PhD.
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