AFF1 (AF4/FMR2 Family Member 1)

P1/2, N=20, Recruiting, University Hospital Tuebingen | Trial completion date: Mar 2027 --> Feb 2029 | Trial primary completion date: Mar 2027 --> Jul 2028

This review highlights the evidence defining its poor prognosis, which is primarily driven by profound chemoresistance to conventional therapies, including glucocorticoids. Finally, we discuss the rapidly evolving therapeutic landscape, detailing the limitations of standard intensive chemotherapy and the immense promise of novel targeted strategies, such as Menin inhibitors (e.g., Revumenib), DOT1L inhibitors, and immunotherapies (e.g., CAR-T cells, Blinatumomab), which hold the potential to revolutionize outcomes for this high-risk leukemia subtype.

These findings indicate that the CNS niche imposes selective pressures that cause lasting metabolic and functional reprogramming of leukemic cells, impairing their ability to reestablish systemic disease and potentially affecting immune cell interactions. Furthermore, these findings may be more generally relevant to primary mixed-lineage infant leukaemia and, increasingly important, lineage-switched infant leukaemia.

The patient was diagnosed with AML with an 11q23 KMT2A::AFF1 gene rearrangement-a mutation increasingly associated with a poor prognosis. This case underscores the importance of recognizing hyperpigmentation as a rare but potential manifestation of LC, especially in younger patients, and highlights the need for prompt diagnosis and intervention to improve patient outcomes.

It highlights an unusual and serious pattern of relapse in an extramedullary site following blinatumomab therapy. Clinicians should remain vigilant for signs of lineage switch and extramedullary disease during treatment, particularly in patients with KMT2A-rearranged B-ALL, and consider imaging or biopsy when new neurologic or systemic symptoms arise.

Thus, the CRISPR/Cas9 technique allowed us to create a bona fide model system to study the very early steps of leukemia onset at the molecular level. In conclusion, this approach is the fastest way to investigate and characterize KMT2A-r fusions in primary human cells.

The biochips achieved detection limits ranging from 9 to 29 copies of the oncogenes using label-free detection in 15 min. Therefore, the biochips developed in this study exhibit promising characteristics for the diagnosis of clinically relevant oncogenes.

Future studies will need to clarify more broadly which genomic/epigenomic alterations drive upfront resistance. Regardless of mechanism, our data supports using Menin-inhibitors upfront or in early lines of therapy before substantial genomic or epigenomic evolution has occurred.

We also found a correlation between the presence of hyperdiploidy and ETV6::RUNX1 and changes in the expression of particular markers. The obtained results demonstrate that CD86 and CD72 can be successfully used as additional markers for MRD assessment in BCP-ALL.

The targeted sequencing approach can help in detecting known and novel fusions in B-ALL, novel breakpoints in the known fusions, gene deletions as oncogenic/novel isoforms and CRLF2 expression.