Fig. 1.

Gain of recurrent KDM6A mutations at relapse and change in KDM6A RNA and protein expression at relapse. a Schematic overview of KDM6A protein structure (NP_066963.2) and mutations (red = truncating; black = missense) identified at diagnosis in 20 AML patients, illustrated using IBS software [40]. Location of mutations is displayed and amino-acid positions are indicated below the graph. Asterisk (*) signifies two patients harboring two mutations each. Presented KDM6A mutations are from AMLCG-99 trial (NCT00266136), AMLCG-2008 trial (NCT01382147), a CN-AML diagnosis-relapse cohort [3] and this work. TRP tetratricopeptide repeat, JmjC Jumonji C. b Comparison of variant allele frequency (VAF) between diagnosis and relapse in 5 AML patients with KDM6A mutations. Due to variations in blast count, VAF was calculated relative to the respective blast count. Raw data for mutation L1130R and V1113Sfs*38 originate from our previous study [3]. c, Immunoblotting for KDM6A expression in five AML patients at diagnosis (D) and relapse (R). Their respective gender is shown on top and the UPN is displayed below. MW, molecular weight; β-actin, loading control. d Comparison of KDM6A protein expression in nine AML patients without KDM6A mutations at diagnosis and relapse. The ratio of KDM6A to β-actin expression is displayed. Respective values at relapse were normalized to the corresponding diagnosis sample. e Pie chart illustrating the regulation of KDM6A mRNA expression in 35 CN-AML patients. The three groups, KDM6A-up, KDM6A-down and KDM6A-no change were defined as a change in expression between diagnosis and relapse of above or below 20%, respectively