TLX1 (T Cell Leukemia Homeobox 1)

Clinically, newly diagnosed patients, most treated with venetoclax based regimens, achieved high remission rates. Our data delineate the structural diversity of BCL11B rearrangements identified by OGM and show that BCL11B activation cannot be reliably inferred from partner gene identity alone. BCL11B immunohistochemistry as a practical surrogate for assessing BCL11B activation is recommended in routine practice.

Importantly, survival analysis revealed that non-TCR TLX1+ patients had significantly poorer outcomes compared to their TCR TLX1⁺ counterparts (3y-OS: 55% vs. 90%, P < 0.001 and 3y-DFS: 45% vs. 75%, P = 0.02). These findings, consistent with our previous observations in TAL1-driven T-ALL, confirm that the clinico-biological impact of an oncogene is influenced by the specific mechanism underlying its deregulation.

Acute respiratory failure, sepsis, and severe infections were the primary reasons for ICU admission. Heart failure, CRRT, and APACHE II score ≥20 were identified as independent risk factors for mortality, while vasopressor use was an independent risk factor for OS.

Initial management included hydroxyurea and liver-protective therapies; however, liver dysfunction progressed despite treatment. With the patient's liver function deteriorating, chemotherapy with venetoclax and azacitidine was initiated under close monitoring, along with intensive supportive care including methylprednisolone...As the leukemic burden decreased, liver function gradually improved, and the patient achieved hematologic recovery sufficient for discharge. This case highlights the challenges of treating elderly AML-M5 patients with hepatic infiltration and emphasizes the importance of early recognition and individualized treatment strategies and the potential benefits of dose-adjusted induction therapy tailored according to the hepatotoxicity profiles of the drugs and the patient's hepatic function.

Additional genetic alterations, termed "secondary hits" are involved in lymphoid development and pathogenesis of ALL. The most frequently observed rearrangements in TCF3 are: PAX5, IKZF1, SETDB2, EBF1, as well as CDKN2A/B.

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.

Cox regression analysis showed that HOX11 was an independent risk factor affecting PFS (p = 0.041). These findings are the first to demonstrate an association between HOX11 overexpression and recurrent B-ALL.

This was further supported by analyses of data from the COG AALL0434 trial, enhancing our understanding of T-ALL in infants/toddlers. Large-scale collaborative studies remain essential to confirm these findings and refine treatment strategies.

WTEa offers a unifying tool to provide a genetic classification of T-ALL/LBLs. If introduced in multicenter prospective studies, it will facilitate the evaluation of the clinical impact of genetic classification.

We observed a strong difference in ERG expression between pediatric T- and B-ALL cases. In conclusion, we confirmed CK2 as a prognostic marker and a therapeutic target.

These findings suggest that ZFP69B promotes the proliferation of HCC cells by directly upregulating the expression of TLX1 and the ensuing TRAPPC9.

To our knowledge this is the largest cohort of adult T-ALL patients characterized by transcriptome sequencing with meaningful clinical follow-up. Risk classification based on molecular subgroups might emerge and contribute to improvements in outcome.