TAL1 (TAL BHLH Transcription Factor 1)

Our study has shown that FBXO32 facilitates HCC growth and metastasis via the PTEN/PI3K/AKT signaling through ubiquitination of TAL1. Consequently, FBXO32 emerges as a promising target for therapeutic intervention in the treatment of HCC.

Our results from primary AML specimens and functional analyses of AML cell lines supports an essential role for the LTMC in AML. Targeting the complex or downstream effectors could provide novel therapeutic considerations for a subset of patients with AML.

Despite multiple cycles of azacitidine, within one month, the patient had transitioned into sAML with blasts increased to 55% with heterogeneity in the sample, and TMEM91::TAL1 expression increased to 2.83%...This case illustrates the value of comprehensive molecular profiling, including RNA-seq, in cases of rapidly progressive MDS that cannot be diagnosed through standard molecular diagnostics. The temporal relationship between expression of the fusions and disease progression warrants additional studies of TMEM91::TAL1 in myeloid malignancies.

No significant difference was found on clinical features and prednisone response between groups at TP0-TP3 (all P>0.05)... Monitoring SIL::TAL1 fusion transcripts can reflect the clinical treatment response. The level of SIL::TAL1 fusion transcripts at early period can predict long-term outcomes of these patients.

DNMT3B activates glycolysis and promotes NSCLC progression by mediating methylation modification of TAL1 and inducing PKM2 transcription.

The Sphingomyelin Synthase 1 gene ( SGMS1 ) is a novel direct target of GATA1 and TAL1. High SGMS1 levels are associated with high GATA1/TAL1 expression and regulate cell cycle progression through the G2/M checkpoint in GATA1 + erythroleukemic Acute Myeloid Leukemia Hel cells. High SGMS1 is associated with lower probability of survival of patients with Acute Myeloid Leukemia and down-regulation of SGMS1 co-operates with microtubule targeting agents to induce cytotoxicity in GATA1 positive AML Hel cells.

In PDX analysis, monoallelic TAL1 expression was stable, contrary to biallelic expression which mostly derived from residual non-malignant haematopoietic cells. Importantly, we report 5 novel TAL1 dysregulation mechanisms using long-read nanopore and OGM analysis, and show that TAL1 hypomethylation identifies TAL1 dysregulation, and is associated with worse prognosis.

An IGH::DUX4 fusion previously found by RNA-seq in Case 3 was not confirmed because DUX4, which has multiple pseudogenes, was refractory to OGM and WGS analyses. OGM is a fundamental tool that complements G-banding analysis in identifying complex SVs in leukemia samples, and WGS effectively closes the gaps in OGM mapping.

The T-ALL with STIL-TAL1 fusion exhibits unique clinical, immunologic, and genetic characteristics. Further multi-center studies, incorporating cytogenetic and molecular analyses, are needed to elucidate the detailed pathophysiology, characteristics, and clinical significance of this gene rearrangement.

Despite achieving remission with intensive chemotherapy, the patient experienced rapid relapse and poor overall survival, reflecting the ineffectiveness of conventional treatments. The findings highlight the synergistic role of SIL-TAL1 and t(11;14) in disease progression and underscore the urgent need for targeted therapies and immunotherapies to improve outcomes in such high-risk cases.

Together, our findings suggested that BLACE gene specifically expressed in B-cell ALL could serve as a new therapeutic target. Further investigations are required to get a comprehensive understanding of the BLACE gene mechanism.

In addition, we found that APTO-253, a small molecule inducer of KLF4, exerts an anti-leukemic effect by targeting SE-driven TAL1 expression in T-ALL cells. Taken together, our results suggest that the induction of KLF4 is a promising strategy to control TAL1 expression and could be a novel treatment for T-ALL patients with a poor prognosis.