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The efficacy and safety of nelarabine in relapsed or refractory T-cell acute lymphoblastic leukemia: a systematic review and meta-analysis.
Ann Hematol
January 2025
Department of Research, Medical Research Circle, Goma, 73 Gisenyi, Democratic Republic of the Congo.
T-cell Acute Lymphoblastic Leukemia (T-ALL) is a subtype of acute lymphoblastic leukemia characterized by the proliferation of abnormal T-cell precursors. Nelarabine, a purine analog, has been approved as a targeted therapy for patients with refractory or relapsed T-ALL. This study aims to evaluate the efficacy and safety of Nelarabine, either as monotherapy or in combination with other therapies, in treating T-ALL.
View Article and Find Full Text PDFCAR-T Therapy Beyond B-Cell Hematological Malignancies.
Cells
January 2025
Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy.
Despite the advances of CAR-T cells in certain hematological malignancies, mostly from B-cell derivations such as non-Hodgkin lymphomas, acute lymphoblastic leukemia and multiple myeloma, a significant portion of other hematological and non-hematological pathologies can benefit from this innovative treatment, as the results of clinical studies are demonstrating. The clinical application of CAR-T in the setting of acute T-lymphoid leukemia, acute myeloid leukemia, solid tumors, autoimmune diseases and infections has encountered limitations that are different from those of hematological B-cell diseases. To overcome these restrictions, strategies based on different molecular engineering platforms have been devised and will be illustrated below.
View Article and Find Full Text PDFDNTT-mediated DNA Damage Response Drives Inotuzumab Ozogamicin Resistance in B-cell Acute Lymphoblastic Leukemia.
Blood
December 2024
St. Jude Children's Research Hospital, Memphis, Tennessee, United States.
Inotuzumab Ozogamicin (InO) is an antibody-calicheamicin conjugate with striking efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, there is wide inter-patient variability in treatment response, and the genetic basis of this variation remains largely unknown. Using a genome-wide CRISPR screen, we discovered the loss of DNTT as a primary driver of InO resistance.
View Article and Find Full Text PDFInhibiting H3K27 Demethylases Downregulates CREB-CREBBP, Overcoming Resistance in Relapsed Acute Lymphoblastic Leukemia.
Cancer Med
January 2025
Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Background: CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti-tumor effects have previously been demonstrated for GSK-J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers.
View Article and Find Full Text PDFFrontline immunotherapeutic combination strategies in adult B-cell acute lymphoblastic leukemia: reducing chemotherapy intensity and toxicity and harnessing efficacy.
Leuk Lymphoma
January 2025
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Using immunotherapeutic agents like inotuzumab ozogamicin (InO), blinatumomab, or chimeric antigen receptor T (CAR T)-cell therapy in frontline adult B-cell acute lymphoblastic leukemia (B-ALL) therapy is promising. These agents are mostly well tolerated and have different toxicity profiles than conventional chemotherapy, enabling their combination with chemotherapy. Additionally, they have often been shown to overcome the traditional adverse ALL risk features.
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