Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome

To evaluate internal tandem duplication (ITD) insertion sites and length as well as their clinical impact in younger adult patients with FLT3 -ITD–positive acute myeloid leukemia (AML), sequencing after DNA-based amplification was performed in diagnostic samples from 241 FLT3 -ITD–mutated patients. All patients were treated on 3 German-Austrian AML Study Group protocols. Thirty-four of the 241 patients had more than 1 ITD, leading to a total of 282 ITDs; the median ITD length was 48 nucleotides (range, 15-180 nucleotides). ITD integration sites were categorized according to functional regions of the FLT3 receptor: juxtamembrane domain (JMD), n = 148; JMD hinge region, n = 48; beta1-sheet of the tyrosine kinase domain-1 (TKD1), n = 73; remaining TKD1 region, n = 13. ITD length was strongly correlated with functional regions ( P ), and AMLSG 07-04 ([NCT00151242][2]; ). [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00146120&atom=%2Fbloodjournal%2F114%2F12%2F2386.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00151242&atom=%2Fbloodjournal%2F114%2F12%2F2386.atom