👤 Walter Fiedler

We present the case of a 60-year-old male patient with a common B-cell acute lymphoblastic leukemia (ALL) who carried the rare t(8; 22)(p11; q11) The presence of the t(8; 22)(p11; q11) The patient was treated according to the German Multicenter ALL (GMALL) Study Group consensus recommendations. The disease was refractory to the first cycle of induction chemotherapy. However, after the second induction, cytological remission was achieved. Nevertheless, minimal residual disease (MRD) positivity persisted (IGH rearrangement detected by PCR) after the first consolidation therapy, giving indication for a stem cell transplantation (SCT). Thirty days post-transplant, no MRD was detected, and complete chimerism was measured for the months following transplantation. However, the patient died in the context of severe graft-versus-host disease and infectious complications 6 months after the SCT. This case highlights the importance of detailed molecular analysis in the initial diagnostics of ALL. Identification of specific chromosomal translocations can provide critical insights for risk assessment and aid decision-making in intensify therapeutic approaches. ClinicalTrials.gov identifier: NCT03011372, NCT04659616. Show less

The conserved multiple PDZ-domain containing protein PATJ stabilizes the Crumbs-Pals1 complex to regulate apical-basal polarity and tight junction formation in epithelial cells. However, the molecular mechanism of PATJ's function in these processes is still unclear. In this study, we demonstrate that knockout of PATJ in epithelial cells results in tight junction defects as well as in a disturbed apical-basal polarity and impaired lumen formation in three-dimensional cyst assays. Mechanistically, we found PATJ to associate with and inhibit histone deacetylase 7 (HDAC7). Inhibition or downregulation of HDAC7 restores polarity and lumen formation. Gene expression analysis of PATJ-deficient cells revealed an impaired expression of genes involved in cell junction assembly and membrane organization, which is rescued by the downregulation of HDAC7. Notably, the function of PATJ regulating HDAC7-dependent cilia formation does not depend on its canonical interaction partner, Pals1, indicating a new role of PATJ, which is distinct from its function in the Crumbs complex. By contrast, polarity and lumen phenotypes observed in Pals1- and PATJ-deficient epithelial cells can be rescued by inhibition of HDAC7, suggesting that the main function of this polarity complex in this process is to modulate the transcriptional profile of epithelial cells by inhibiting HDAC7. Show less