Thursday, January 04, 2018 -- Acute myeloid leukemia (AML) therapy is guided mainly by cytogenetic profile, such as chromosomal duplication or deletion, and molecular mutations. FLT3 mutations are the most common genetic abnormalities detected in patients with AML and are usually associated with a high relapse rate and short overall survival. Given the dismal outcomes in patients with FLT3-mutant AML, a great effort has been underway over the last several years to develop clinically effective FLT3 inhibitors.
Wednesday, January 03, 2018 -- In a unique clinical trial, a group of oncologists with experience treating acute promyelocytic leukemia are making themselves available around the clock to help clinicians at hospitals across the country treat their APL patients.
Tuesday, January 02, 2018 -- NICE will re-assess Pfizer’s blood cancer drug Besponsa after the company successfully appealed a decision rejecting regular NHS funding last summer. Pfizer said a NICE committee will re-assess evidence for Besponsa (inotuzumab ozogamicin), approv...
Thursday, January 04, 2018 -- A team of researchers in Italy and Austria has determined that a drug approved to treat chronic lymphocytic leukemia (CLL) may be less effective in a particular subset of patients.
Thursday, January 04, 2018 -- NewsCX-01 is an investigational agent that has the potential to enhance the effectiveness of leukemia treatments by disrupting the adhesion of leukemia cells in the protective bone marrow environment.Contributed Author: Cantex Pharmaceuticals, Inc.Topics: Drug Development
Wednesday, January 03, 2018 -- Purpose: Leukemia stem cells (LSCs) are an important source of tyrosine kinase inhibitor resistance and disease relapse in patients with chronic myelogenous leukemia (CML). Targeting LSCs may be an attractive strategy to override this thorny problem. Given that EZH2 was overexpressed in primary CML CD34+ cells, our purpose in this study was to evaluate the effects of targeting EZH2 on CML LSCs and clarify its underlying mechanism. Experimental Design: Human primary CML CD34+ cells and retrovirally BCR–ABL-driven CML mouse models were employed to evaluate the effects of suppression of EZH2 by GSK126- or EZH2-specific shRNA in vitro and in vivo. Recruitment of EZH2 and H3K27me3 on the promoter of tumor-suppressor gene PTEN in CML cells was measured by chromatin
Wednesday, January 03, 2018 -- Purpose: fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is present in 30% of acute myeloid leukemia (AML), and these patients have short disease-free survival. FLT3 inhibitors have limited and transient clinical activity, and concurrent treatment with inhibitors of parallel or downstream signaling may improve responses. The oncogenic serine/threonine kinase Pim-1 is upregulated downstream of FLT3-ITD and also promotes its signaling in a positive feedback loop, suggesting benefit of combined Pim and FLT3 inhibition. Experimental Design: Combinations of clinically active Pim and FLT3 inhibitors were studied in vitro and in vivo. Results: Concurrent treatment with the pan-Pim inhibitor AZD1208 and FLT3 inhibitors at clinically applicable concentrations abrogated in vitro growth of FLT3-ITD, but not wild-type FLT3 (FLT3-WT), cell lines.
Thursday, January 04, 2018 -- Leukemia relapse remains the major cause of allogeneic hematopoietic stem cell transplantation (HCT) failure, and the prognosis for patients with post-HCT relapse is poor. There is compelling evidence that potent selective antileukemic effects can be delivered by donor T cells specific for particular minor histocompatibility (H) antigens. Thus, T-cell receptors (TCRs) isolated from minor H antigen–specific T cells represent an untapped resource for developing targeted T-cell immunotherapy to manage post-HCT leukemic relapse. Recognizing that several elements may be crucial to the efficacy and safety of engineered T-cell immunotherapy, we developed a therapeutic transgene with 4 components: (1) a TCR specific for the hematopoietic-restricted, leukemia-associated minor H antigen, HA-1; (2) a CD8 coreceptor to promote function of the class I–restricted
Thursday, January 04, 2018 -- Most patients with acute myeloid leukemia (AML) can only be cured when allogeneic hematopoietic stem-cell transplantation induces a graft-versus-leukemia immune response (GVL). Although the role of T cells and natural killer cells in tumor immunology has been established, less is known about the contribution of B cells. From B cells of high-risk patients with AML with potent and lasting GVL responses, we isolated monoclonal antibodies directed against antigens expressed on the cell surface of AML cells but not on normal hematopoietic and nonhematopoietic cells. A number of these donor-derived antibodies recognized the U5 snRNP200 complex, a component of the spliceosome that in normal cells is found in the cell. In AML however, the U5 snRNP200 complex is exposed on