Conformational Control Inhibition of the BCR-ABL1 Tyrosine Kinase, Including the Gatekeeper T315I Mutant, by the Switch-Control Inhibitor DCC-2036
Using structure-based drug design, scientists developed compounds that bind to residues (Arg386/Glu282) ABL1 uses to switch between inactive and active conformations. [Cancer Cell] Adult Hematopoiesis Is Regulated by TIF1γ, a Repressor of TAL1 and PU.1 Transcriptional Activity
Researchers showed that deletion of TIF1γ in adult hematopoiesis is compatible with life and long-term maintenance of essential blood cell lineages. [Cell Stem Cell]
Prostaglandin E2 Enhances Human Cord Blood Stem Cell Xenotransplants and Shows Long-Term Safety in Preclinical Nonhuman Primate Transplant Models
Investigators described preclinical analyses of the therapeutic potential of dimethyl-prostaglandin E2 treatment by using human and nonhuman primate hematopoietic stem cells. [Cell Stem Cell]
A Novel TNFR1-Triggered Apoptosis Pathway Mediated by Class IA PI3Ks in Neutrophils
Scientists reported surprising differences in the molecular mechanisms used for caspase activation between FAS/CD95- and TNF receptor 1 (TNFR1)-stimulated neutrophils. [Blood]
SMAD4 Binds HOXA9 in the Cytoplasm and Protects Primitive Hematopoietic Cells Against Nuclear Activation by HOXA9 and Leukemia Transformation
Investigators studied leukemic stem cells in a Smad4-/- mouse model of acute myelogenous leukemia induced either by the HOXA9 gene or by the fusion oncogene NUP98-HOXA9. [Blood]
Protein Disulfide Isomerase Blocks CEBPA Translation and Is Upregulated During the Unfolded Protein Response in Acute Myeloid Leukemia
Scientists screened for additional CEBPA mRNA binding proteins and they identified protein disulfide isomerase, an endoplasmic reticulum resident protein, to bind to the CEBPA mRNA stem loop region. [Blood]
TNF-α–Dependent Loss of IKKβ-Deficient Myeloid Progenitors Triggers a Cytokine Loop Culminating in Granulocytosis
Investigators identified a regulatory cytokine loop that causes neutrophilia in Ikkβ−deficient mice. [Proc Natl Acad Sci USA]
HDAC Inhibitors Potentiate the Activity of the Bcr/Abl Kinase Inhibitor KW-2449 in Imatinib-Sensitive and -Resistant Bcr/Abl+ Leukemia Cells In Vitro and In Vivo
The purpose of this study was to determine whether HDAC inhibitors such as vorinostat or entinostat (SNDX-275) could increase the lethality of the dual Bcr/Abl-aurora kinase inhibitor KW-2449 in various Bcr/Abl+ human leukemia cells, including those resistant to imatinib mesylate. [Clin Cancer Res]
CLINICAL RESEARCH
Integrated Transcript and Genome Analyses Reveal NKX2-1 and MEF2C as Potential Oncogenes in T Cell Acute Lymphoblastic Leukemia
To identify oncogenic pathways in T cell acute lymphoblastic leukemia, scientists combined expression profiling of 117 pediatric patient samples and detailed molecular-cytogenetic analyses including the Chromosome Conformation Capture on Chip method. [Cancer Cell]
Mutations in ANKRD26 Are Responsible for a Frequent Form of Inherited Thrombocytopenia: Analysis of 78 Patients from 21 Families
Researchers recently identified mutations in the 5’UTR region of ANKRD26 gene in 9 thrombocytopenia 2 families. Here they report on 12 additional pedigrees with ANKRD26 mutations, 6 of which are new. [Blood]
The Addition of Arsenic Trioxide to Low-Dose Ara-C in Older Patients with Acute Myeloid Leukemia Does Not Improve Outcome
Investigators report a randomized trial of low-dose Ara-C (LDAC) versus LDAC and arsenic trioxide. [Leukemia]