Abstract
Acute Myeloid Leukemia (AML) with rearranged PICALM::MLLT10 is a rare and poorly characterized entity. Here, we describe a patient with this rearrangement, and compare this case to the literature. We observed a trend towards young age, male sex, extramedullary involvement (particularly mediastinal myelosarcoma), trisomy 4, trisomy 19 and aberrant CD7-expression. It was suggested that upregulation of DOT1l or BMI1 is a key effector for subsequent leukemogenesis. However, molecular data are not available for most published cases. Interestingly, two different EZH2-mutations were detected in our case, while generally being rare in AML, which is concordant with recent reports on the occurrence of EZH2mut in this AML subtype. As a synergistic effect of BMI1 and EZH2 has already been demonstrated in other neoplasms, we hypothesize that acquiring an EZH2 mutation might be a crucial proliferation advantage in PICALM::MLLT10 positive cells. This may explain the high percentage of EZH2 mutated cases in this entity, but also supports the hypothesis of BMI1-mediated leukemogenesis.