MLLT1 (MLLT1 Super Elongation Complex Subunit)

In this case, we report the recurrence of nephroblastoma with MLLT1 gene mutation and review relevant literature. The studies on molecular genetic mechanism will provide a theoretical basis for early warning, optimize individualized treatment plan, and are important for improving prognosis.

The EC-NDC assay is a robust tool providing a single end-to-end workflow for the simultaneous detection of MRD markers, selected translocations, and sequence variants in ALL and Burkitt leukaemia.

Although HMGA1 might have little effect on normal hematogenesis, it seemed that HMGA1 had inhibitory effect on ATRA-induced differentiation process of MLL-ENL leukemic cells. Though more conditions including AML types and differentiation methods should be tested and the molecular mechanisms should be scrutinized, there is a possibility that inhibition of HMGA1 is effective in combination with differentiation treatments.

Therapeutically, YEATS containing MLL-ENL leukemic cells display increased sensitivity to the YEATS inhibitor SGC-iMLLT compared to control AML cells. Our results demonstrate that the YEATS domain is important for MLL-ENL fusion protein-mediated leukemogenesis and exposes an "Achilles heel" that may be therapeutically targeted for treating t(11;19) patients.

By using human AML datasets, overexpression of EVI1 and CCND1 were associated with IFN-γ signature, including up-regulation of STAT1 and CD274, and elevated expression of chemokines, with increased exhaustion molecules in T cells. These data collectively suggest that cyclin D1 is implicated in the development of EVI1-AML through the formation of IFN-γ signature and exhausted T cell phenotypes, which could be potentially targeted.

Mechanistically, the mutation interrupted the stability of moesin and conferred a neomorphic activity to the protein, which converged on enhanced extracellular signal-regulated kinase activity. Thereby, our studies demonstrate a critical role of ERM proteins in AML, with implications also for human cancer.

We discovered a potentially harmful frameshift deletion at Gln461fs in the MLLT1 gene. Further investigation is required to confirm the presence of the identified mutations in patient tissue samples, as well as the significance of the frameshift mutation in the MLLT1 gene on GBM biology and response to therapy based on genomic functional experiments.

Our results demonstrated a spectrum of cytogenetically cryptic NUP98 rearranged acute leukemia in children and young adults with poor prognosis, co-operation between NUP98-NSD1 fusion and FLT3-ITD in AML whereas novel NUP98-MLLT1 fusion and other gene mutations in ALAL-NOS. Importantly, caution is required in interpreting FISH result of the NUP98 probe and abnormal finding to be confirmed by NGS study. Remarkably, our case with apparently false NUP98 alteration exhibited the characteristic feature of a rare subtype of pediatric AML carrying a cytogenetically cryptic CBFA2T3-GLIS2 fusion: a peculiar immunophenotype and dismal prognosis.