Abstract:
:Although virtually all pediatric patients with acute myeloid leukemia (AML) achieve a complete remission after initial induction therapy, 30%-40% of patients will encounter a relapse and have a dismal prognosis. To prevent relapses, personalized treatment strategies are currently being developed, which target specific molecular aberrations. To determine relevance of established AML type I/II mutations that may serve as therapeutic targets, we assessed frequencies of these mutations and their persistence during disease progression in a large group (n = 69) of paired diagnosis and relapse pediatric AML specimens. In 26 of 42 patients (61%) harboring mutations at either stage of the disease, mutation status changed between diagnosis and relapse, particularly in FLT3, WT1, and RAS genes. Presence or gain of type I/II mutations at relapse was associated with a shorter time to relapse (TTR), whereas absence or loss correlated with longer TTR. Moreover, an adverse outcome was found for patients with activating mutations at relapse, which was statistically significant for FLT3/ITD and WT1 mutations. These findings suggest that mutational shifts affect disease progression. We hence propose that risk stratification, malignant cell detection, and selection of personalized treatment should be based on status of type I/II mutations both at initial diagnosis and during follow-up.
journal_name
Bloodjournal_title
Bloodauthors
Bachas C,Schuurhuis GJ,Hollink IH,Kwidama ZJ,Goemans BF,Zwaan CM,van den Heuvel-Eibrink MM,de Bont ES,Reinhardt D,Creutzig U,de Haas V,Assaraf YG,Kaspers GJ,Cloos Jdoi
10.1182/blood-2010-03-276519subject
Has Abstractpub_date
2010-10-14 00:00:00pages
2752-8issue
15eissn
0006-4971issn
1528-0020pii
blood-2010-03-276519journal_volume
116pub_type
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