FLT3‐ITD + WT1 mutation

Cooperating FLT3-ITD and WT1 mutations define NUP98-NSD1, and chromosome 13 aberrations are highly enriched in NUP98-KDM5A. Importantly, we demonstrate that NUP98 fusions portend dismal overall survival, with the noteworthy exception of patients bearing abnormal chr13.

This analysis of a large cohort of adult patients with newly diagnosed AML revealed that UBTFmutations can be found in about 1% of all patients with AML, but are considerably more common in young adults. As in pediatric patients, they are associated with a specific cytogenetic and molecular profile, i.e. high rate of +8, FLT3-ITD and WT1 mutations. As a novel finding, adult UBTF-TD patients frequently showed signs of myelodysplasia.

Type of donor, stem cell source and conditioning regimen did not differ between the 2 groups, 74% of pts received a busulfan, cyclophosphamide and melphalan conditioning. UBTF-TDs were detected in 25 of the 104 pts (24%; 16 males/9 females), while 79 pts (76%; 45 males, 34 females) showed no UBTF mutation (UBTF-wt). Variant allelic frequencies of UBTF-TD ranged from 11%-79% (median 41%). Median age at diagnosis in UBTF-TD and UBTF-wt pts was not different (11.0 vs.

In this issue of Blood Cancer Discovery, Dr Masayuki Umeda and colleagues identify and comprehensively analyze a novel recurrent UBTF mutation (tandem duplications) in pediatric acute myeloid leukemia. Acute myeloid leukemia cases with UBTF tandem duplications display distinctive biologic features, including association with FLT3-ITD and WT1 mutations and high-risk disease, and appear to represent a new genetic subtype of acute myeloid leukemia.

Regarded as the desirable characteristic, the present study is generally distinguished by the similar previous ones due to assessing the FFPE BM tissue from the perspective of the type of assessed sample. This discrepancy between our results and those in prior studies may be due to the disparity of the studied population size, adopted methods as well as the sample type. In this survey, regarding to low amount of extracted DNA from the paraffinized samples, the HRM method was efficient in determining the mentioned mutations.

Multivariate analysis demonstrated that WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). In conclusion, our findings have demonstrated that WT1 mutations are independent poor prognostic factors in pediatric AML.