Clinicopathologic features and outcomes of acute leukemia harboring PICALM::MLLT10 fusion.

ABSTRACT

The PICALMMLLT10 fusion is a rare but recurrent cytogenetic abnormality in acute leukemia, with limited clinicopathologic and outcome data available. Herein, we analyzed 156 acute leukemia patients with PICALMMLLT10 fusion, including 12 patients from our institutions and 144 patients from the literature. The PICALMMLLT10 fusion preferentially manifested in pediatric and young adult patients, with a median age of 24 years. T-lymphoblastic leukemia/lymphoma (T-ALL) constituted 65% of cases, acute myeloid leukemia (AML) 27%, and acute leukemia of ambiguous lineage (ALAL) 8%. About half of T-ALL were classified as an early T-precursor (ETP)-ALL. In our institutions' cohort, mediastinum was the most common extramedullary site of involvement. Eight of 12 patients were diagnosed with T-ALL exhibiting a pro-/pre-T stage phenotype (CD4/CD8-double negative, CD7-positive), and frequent CD79a expression. NGS revealed pathogenic mutations in 5 of 6 tested cases, including NOTCH1, and genes in RAS and JAK-STAT pathways and epigenetic modifiers. Of 138 cases with follow-up, pediatric patients (<18 years) had 5-year overall survival (OS) of 71%, significantly better than adults at 33%. The 5-year OS for AML patients was 25%, notably shorter than T-ALL patients at 54%; this distinction was observed in both pediatric and adult populations. Furthermore, adult but not pediatric ETP-ALL patients demonstrated inferior survival compared to non-ETP-ALL patients. Neither karyotype complexity nor transplant status had a discernible impact on OS. In conclusion, PICALMMLLT10 fusion is most commonly seen in T-ALL patients, particularly those with an ETP phenotype. AML and adult ETP-ALL patients had adverse prognosis. PICALMMLTT10 fusion testing should be considered in T-ALL, AML, and ALAL patients.