Beschreibung:
<jats:title>Abstract</jats:title><jats:p>A large variety of molecular rearrangements of the <jats:italic>NUP98</jats:italic> gene have been described in the past decades (n = 72), involving fusion partners coding for different transcription factors, chromatin modifying enzymes, as well as various cytosolic proteins. Here, we report the case of an AML‐M2 patient with a variant <jats:italic>NUP98‐LEDGF/PSIP1</jats:italic> gene fusion (N9‐L10). In this patient, three different<jats:italic> NUP98-LEDGF</jats:italic> fusion mRNAs were characterized due to alternative splicing in <jats:italic>LEDGF</jats:italic> exon 11. Targeted high‐throughput sequencing revealed the presence of <jats:italic>IDH1</jats:italic>, <jats:italic>SRSF2</jats:italic>, and <jats:italic>WT1</jats:italic> additional pathogenic mutations. To improve the therapeutic monitoring, quantification of <jats:italic>NUP98</jats:italic>‐<jats:italic>LEDGF</jats:italic> mRNA by real‐time PCR was developed. Because of poor response to conventional chemotherapy, allogeneic stem cell transplantation was performed, followed by 20 cycles of azacitidine‐based preemptive treatment of relapse. More than 31 months after diagnosis, corresponding to 25 months post SCT and 4 months after the last cycle of azacytidine, the patient is in complete molecular remission (undetectable <jats:italic>NUP98‐LEDGF</jats:italic> mRNA transcripts). This study highlights the considerable variability in breakpoint location within both <jats:italic>NUP98</jats:italic> and <jats:italic>LEDGF</jats:italic>, associated with alternative splicing affecting <jats:italic>LEDGF</jats:italic>. It also emphasizes the need to fully characterize the breakpoints within the two genes and the identification of all fusion mRNAs, particularly for the development of a molecular monitoring assay. All these data seem critical for the optimal management of <jats:italic>NUP98</jats:italic>‐<jats:italic>LEDGF </jats:italic>+ hematological malignancies commonly associated with a poor prognosis.</jats:p>