A higher-order configuration of the heterodimeric DOT1L-AF10 coiled-coil domains potentiates their leukemogenenic activity Biochemistry
Chromosomal translocations of MLL1 (Mixed Lineage Leukemia 1) yield oncogenic chimeric proteins containing the N-terminal portion of MLL1 fused with distinct partners. The MLL1–AF10 fusion causes leukemia through recruiting the H3K79 histone methyltransferase DOT1L via AF10’s octapeptide and leucine zipper (OM-LZ) motifs. Yet, the precise interaction sites in DOT1L, detailed...
ConclusionAlthough classically, majority of studies have shown oncogenic roles of nucleoporins as genetic fusion partners in several types of leukemia, emerging evidence suggests that nucleoporins also modulate many cellular signaling pathways that are associated with several major non-hematological malignancies, such as carcinomas of skin, breast, lung, prostate and colon. Hence, nucleoporins are emerging as novel therapeutic targets in human tumors.
Conditions: Acute Myeloid Leukemia; Myelodysplasia Intervention: Biological: NK cells Sponsors: Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Ministry of Health, Italy Not yet recruiting
Conditions: B-cell Acute Lymphoblastic Leukemia (B-ALL); Safety and Efficacy of CD19 UCAR-T Cells Intervention: Biological: CD19 UCARTcells Sponsor: Shanghai Longyao Biotechnology Inc., Ltd. Recruiting
(Sanford Burnham Prebys Medical Discovery Institute) Scientists at Sanford Burnham Prebys Medical Discovery Institute have identified a combination of two anti-cancer compounds that shrank pancreatic tumors in mice -- supporting the immediate evaluation of the drugs in a clinical trial. US Food and Drug Administration (FDA)-approved versions of the compounds are used today to treat certain leukemias and solid tumors, including melanoma. The study was published in Nature Cell Biology.
Leukemia, Published online: 18 November 2019; doi:10.1038/s41375-019-0639-xRIG-I-based immunotherapy enhances survival in preclinical AML models and sensitizes AML cells to checkpoint blockade
Leukemia, Published online: 18 November 2019; doi:10.1038/s41375-019-0646-yBRAF inhibitor treatment in classic hairy cell leukemia: a long-term follow-up study of patients treated outside clinical trials
Leukemia, Published online: 18 November 2019; doi:10.1038/s41375-019-0644-0Stat3 mutations impact on overall survival in large granular lymphocyte leukemia: a single-center experience of 205 patients
Leukemia, Published online: 18 November 2019; doi:10.1038/s41375-019-0632-4Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry
High WT1 expression after allogeneic hematologic stem cell transplantation (allo-HSCT) can strongly predict relapse in acute myeloid leukemia (AML). However, the cutoff values obtained were inconsistent. The precise cutoff values may be optimized through subtype analysis, and the RUNX1-RUNX1T1 fusion transcript provides an ideal reference. RUNX1-RUNX1T1 and WT1 transcript levels were simultaneously measured in 1,299 bone marrow samples serially collected from 176 t(8;21) AML patients after receiving allo-HSCTfor.