The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR.

Two classes of novel agents, NEDD8-activating enzyme (NAE) and histone deacetylase (HDAC) inhibitors, have shown single-agent activity in acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS). Here we examined mechanisms underlying interactions between the NAE inhibitor pevonedistat (MLN4924) and the approved HDAC inhibitor belinostat in AML/MDS cells. MLN4924/belinostat coadministration synergistically induced AML cell apoptosis with or without p53 deficiency or FLT3-internal tandem duplication (ITD), whereas p53 short hairpin RNA (shRNA) knockdown or enforced FLT3-ITD expression significantly sensitized cells to the regimen.

Co-administration of the mTORC1/TORC2 inhibitor INK128 and the Bcl-2/Bcl-xL antagonist ABT-737 kills human myeloid leukemia cells through Mcl-1 down-regulation and AKT inactivation.

Effects of concurrent inhibition of mTORC1/2 and Bcl-2/Bcl-xL in human acute myeloid leukemia cells were examined. Tetracycline-inducible Bcl-2/Bcl-xL dual knockdown markedly sensitized acute myeloid leukemia cells to the dual TORC1/2 inhibitor INK128 in vitro as well as in vivo. Moreover, INK128 co-administered with the Bcl-2/xL antagonist ABT-737 sharply induced cell death in multiple acute myeloid leukemia cell lines, including TKI-resistant FLT3-ITD mutants and primary acute myeloid leukemia blasts carrying various genetic aberrations e.

T-cell lymphoblastic lymphoma/leukemia presenting as a pituitary mass lesion: a case report and review of the literature.

We present a rare case of primary T-cell lymphoblastic lymphoma of the pituitary gland. A 58-year-old woman presented with headaches, right-sided ptosis and cranial nerve III palsy. She subsequently developed polyuria, polydipsia, and hyperglycemia and was found to have hypopituitarism.

Marginal zone lymphomas involving meningeal dura: possible link to IgG4-related diseases.

Dura-based marginal zone lymphomas represent an uncommon group of low-grade B-cell neoplasms, and literature regarding the clinical, histological and genetic profile of these tumors in the context of the newly described IgG4-related entities is lacking. We analyzed 32 dura-based marginal zone lymphomas identified in 27 females and 5 males ranging in age from 33-82 years (median 50). Morphologic examination, immunohistochemical studies and PCR for B-cell clonality were carried out in all cases.

Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR.

Marginal zone lymphomas present rarely in children and young adults as either primary nodal or extranodal disease and have an excellent prognosis. To date, chromosomal aberrations have not been analyzed in the pediatric and young adult population. We undertook a study to analyze genetic alterations in nodal and extranodal marginal zone lymphomas in children and young adults using fluorescence in situ hybridization (FISH) and RT-PCR.