SEPTIN6 (Septin 6)

This review summarizes the current knowledge about the role of SEPT2 in tumors and supports its potential as a biomarker for certain types of tumors. After in-depth analysis, it provides new perspectives for oncology.

Differential expression of most proteins was also associated with shorter transformation-free survival (p < 0.05). These findings emphasize underlying differences in FL biology predictive of subsequent transformation, highlighting deregulation of important interconnected cellular pathways.

We provide evidence to incorporate the five adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcome, and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs.

Concurrent overexpression of Septin8 with Septin11 knockdown HSPC caused a significant increase in the total number of colonies compared to controls (Figure 1). These data indicate an important role of Septin11 in murine hematopoiesis and a potential redundant role for Septin8.

Overall, our data demonstrates the acquisition of de novo gain of function mutations in the SEPTIN6 gene in myelopoiesis and suggests deleterious effects on engrafting hematopoietic stem cells. These mutations are associated with the development of MDS in two pediatric patients.

A promising approach is the use of Azacitidine (Aza) for treatment of molecular relapse which we evaluated within the clinical trial "AMoRe2017"...Conversely, the relatively slow-acting mechanism of epigenetic therapy seems to be ineffective in highly proliferative subgroups of AML with KMT2A-rearrangements or FLT3-ITD. Further studies are mandatory to define treatment options for molecular relapses of non-favorable pediatric AML and to confirm potential improvement of outcome post-HSCT.

These cases exhibited TBL1XR1::RARB and KMT2A::SEPT6 fusions as well as mutations, e.g., NPM1 insertion and non-recurrent chromosomal aberrations. Our findings demonstrate the genetic diversity of AML with APL-like morphological features, which is of high importance for successful therapy implementation.

Engraftment studies demonstrated a significant reduction in bone marrow chimerism in primary transplant recipients after knockdown of Septin-6 most clearly in ST-HSC (Table 2) with a trend towards a decrease in LT-HSC and MPP. These data support a key role of Septin-6 in murine and human hematopoiesis via alterations in cell cycle and validate the pathogenic nature of a specific mutation in human SEPTIN-6.

In conclusion, this case study comprises a unique long-term follow-up of the clonal dynamics underlying two co-existing, distinct and competing SF3B1mt clones which identifies subtle molecular changes and differences underlying the expansion and progression of SF3B1mt clones. *Moura PL, Hofman IJF, Nannya Y and Aliouat A contributed equally to this work.