MT1E in AML: A Gateway to Understanding Regulatory Cell Death and Immunotherapeutic Responses.

Regulated cell death (RCD) plays a crucial role in the initiation and progression of tumors, particularly in acute myeloid leukemia (AML). This study investigates the prognostic importance of RCD-related genes in AML and their correlation with immune infiltration.We combined TCGA and GTEx data, analyzing 1488 RCD-related genes, to develop a predictive model using LASSO regression and survival analysis. The model's accuracy was validated against multiple databases, examining immune cell infiltration, therapy responses, and drug sensitivity among risk groups. RT-qPCR confirmed MT1E expression in AML patients and healthy bone marrow. CCK8 and Transwell assays measured cell proliferation, adhesion, migration, and invasion, while flow cytometry and Western blotting assessed apoptosis and protein expression.We developed a prognostic model using 10 RCD methods, which demonstrated strong predictive ability, showing an inverse correlation between age and risk scores with survival in AML patients. Functional enrichment analysis of the model is linked to immune modulation pathways. RT-qPCR revealed significantly lower MT1E expression in AML versus healthy bone marrow (p<0.05). Consequently, experiments were designed to assess the function of MT1E overexpression.Findings indicated that MT1E overexpression showed it significantly reduced THP-1 cell proliferation and adhesion(p<0.001), decreased migration(p<0.001) and invasiveness(p<0.05), and increased apoptosis(p<0.05), with a notable rise in Caspase3 expression.A novel AML RCD risk model was developed, showing promise as a prognostic marker for evaluating outcomes and immune therapy effectiveness. Insights into MT1E's impact on AML cell proliferation and apoptosis open possibilities for improving patient outcomes and devising personalized treatment strategies.

Long-Term Remission in T315I+ Relapsed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia with Blinatumomab and Allogeneic Stem Cell Transplantation: Two Case Studies.

BACKGROUND Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in adults has a poor prognosis with conventional chemotherapy. Treatment with tyrosine kinase inhibitors (TKIs) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved clinical outcomes; however, the relapse rate is still high. Therapeutic options for patients with relapsed/refractory (R/R) Ph+ ALL are scarce, with very few studies focusing on these patients. Blinatumomab is a novel bispecific T-cell engager antibody construct showing promising efficacy in R/R Ph+ ALL. CASE REPORT Here, we present 2 cases of relapsed Ph+ ALL with T315I mutation refractory to multiple TKIs and chemotherapy. Patient 1 was a 48-year-old woman who had increased leukocytes in her peripheral blood cells, with 90% abnormal cells and decreased platelets. Bone marrow (BM) smear showed 95% blasts. Patient 2 was a 20-year-old man who had leukocytosis with thrombocytopenia, while all other parameters were normal. BM aspirate showed 98% immature granulocytes/blasts. The immunophenotypic observations of both the patients on BM were consistent with the presence of ALL. Both patients were effectively treated with a combination of blinatumomab and allo-HSCT and achieved complete remission in 1 month with minimal residual disease negativity and remained in remission for a long period. CONCLUSIONS The findings suggest, that for patients with R/R Ph+ ALL with T315I mutation who respond poorly to TKIs, salvage therapy with blinatumomab is a potentially effective treatment for improving clinical outcomes. The treatment with blinatumomab can further act as a bridge to HSCT in these patients, helping them to attain deeper remission.

High-dose rituximab in combination with autologous stem cell transplantation for relapsed or refractory diffuse large B cell lymphoma / Combinación de altas dosis de rituximab y autotrasplante de progenitores hematopoyéticos en pacientes de linfoma B difuso de células grandes en recaída o refractario

OBJECTIVES: The aim of this study was to evaluate the efficacy and toxicity of high-dose rituximab (HD-R) in combination with autologous stem cell transplantation (auto-SCT) in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). METHODS: There were 22 patients in the HD-R group, to whom rituximab was administered during stem cell mobilization (375mg/m2 1 day before and 7 days after chemotherapy) and after transplantation (1000mg/m2 on days +1 and +8). In the control group, the procedure was the same as that in the HD-R group but without rituximab. We observed the safety, tolerability, adverse effects and immune reconstitution of HD-R therapy. The log-rank test, univariate analysis and multivariate Cox regression analysis were used to evaluate the effect of HD-R on survival. RESULTS: In total, 22 relapsed or refractory DLBCL patients were treated with HD-R. No dose-limiting toxicities were observed except for CD19+ B cell reconstruction in the first 6 months after SCT. There were 20 relapsed or refractory DLBCL patients in the control group. The 3-year progression-free survival (PFS) and overall survival (OS) greatly improved in the HD-R group compared to that in the control group (63.8% vs. 35.0%, P=0.028 and 80.1% vs. 50.0%, P=0.035, respectively). The univariate and multivariate analyses demonstrated that HD-R and the time to relapse were independent prognostic factors for OS and PFS. CONCLUSION: HD-R in combination with auto-SCT is a feasible and promising treatment for patients with relapsed or refractory DLBCL

OBJETIVOS: El objetivo de este estudio fue evaluar la eficacia y la toxicidad de la combinación de altas dosis de rituximab (HD-R) y el trasplante de células madre autólogas (auto-SCT) en pacientes con linfoma B difuso de células grandes (LBDCG) en recaída o refractario. MÉTODOS: El grupo HD-R incluyó 22 pacientes a quienes se les administró rituximab durante la movilización de células madre (375mg/m2 un día antes y 7 días después de la quimioterapia) y tras el trasplante (1000mg/m2 los días +1 y +8). En el grupo control, el procedimiento fue el mismo que en el grupo HD-R, aunque sin rituximab. Observamos la seguridad, la tolerabilidad, los efectos adversos y la reconstitución inmune de la terapia HD-R. Utilizamos la prueba log-rank, el análisis univariante y el análisis de regresión de Cox multivariante para evaluar el efecto de HD-R en la supervivencia. RESULTADOS: En total, 22 pacientes de LBDCG en recaída o refractario fueron tratados con HD-R. No se observaron toxicidades limitantes de dosis excepto para la reconstrucción de células CD19+ B en los primeros 6 meses tras SCT. El grupo control incluyó 20 pacientes de LBDCG en recaída o refractario. La supervivencia libre de progresión (SLP) a 3 años y la supervivencia general (SG) mejoró significativamente en el grupo HD-R en comparación con el grupo control (63,8 vs. 35%; p = 0,028 y el 80,1 vs. 50%; p = 0,035, respectivamente). Los análisis univariante y multivariante demostraron que HD-R y tiempo de recaída eran factores pronósticos independientes para SG y SLP. CONCLUSIÓN: La combinación de HD-R y auto-SCT es un tratamiento factible y prometedor para pacientes con LBDCG en recaída o refractario