Substances tested

In chemotherapy-induced febrile neutropenia, filgrastim reduced the median days of neutropenia from 4.0 to 3.0 (neutrophil count under 0.5 x 10^9/L, p = 0.005) and time to resolution of febrile neutropenia from 6.0 to 5.0 days (p = 0.01). Days of fever were unchanged at 3.0 in both arms. Risk of hospitalisation beyond 11 days was halved (relative risk 2.1, 95 percent CI 1.1 to 4.1, p = 0.02).

Mice lacking G-CSF have chronic neutropenia with blood neutrophils at 20 to 30 percent of wild type, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilisation. Marrow granulopoietic precursors, the pool that contains the myelocyte, fall by about 50 percent.

All 24 patients with acute promyelocytic leukemia attained complete remission without marrow hypoplasia. In marrow suspension culture 14 of 15 tested patients showed morphological maturation in response to retinoic acid at 1 micromol/L; chloroacetate esterase and alpha-naphthyl acetate esterase staining and electron microscopy confirmed differentiation to granulocytes with functional maturation by nitroblue tetrazolium reduction. Side effects were mild dryness of lips and skin with occasional headache and digestive symptoms. Eight patients relapsed after 2 to 5 months.

The single patient in the series who did not respond to retinoic acid in vitro and was resistant to retinoic acid treatment attained complete remission after low-dose cytosine arabinoside was added. Reported as a single case within the ATRA series.

Genetic ablation and pharmacological inhibition of CysLTR1 diminished tumour growth with enhanced antitumour immunity. The antitumour effect ran through transcriptomic rewiring of granulopoiesis and reprogramming of neutrophils toward an antitumour phenotype, requiring MXD1 and NFE2 to direct myeloid progenitor commitment and differentiation with controlled de novo synthesis of granule cargoes. Targeting CysLTR1 overcame resistance to anti-PD1 in multiple mouse tumour models.

Agranulocytosis requiring hospitalisation was attributed to semaglutide in a single patient and treated with granulocyte colony-stimulating factor. No mechanism at the level of the granulocytic precursor is established by this report.

Six macrocyclic peptides from mRNA-displayed libraries strongly inhibited recombinant and endogenous cell-derived NSP4 and did not inhibit 13 structurally related proteases. Crystal structures of the two most potent inhibitors show binding at the NSP4 active site, with a substrate-like interaction and resistance to hydrolysis resembling the sunflower trypsin inhibitor-1. Research tools, not therapeutics.

A five-basepair deletion in the second exon truncates the 32-kD major isoform with loss of the dimerisation domain, DNA binding region and transcriptional activity. The result is neutrophil-specific granule deficiency: recurrent pyogenic infections, defective chemotaxis and bactericidal activity, and absent secondary granule proteins. This establishes C/EBP epsilon as required for the promyelocyte to myelocyte transition. Listed here because it is the molecular switch any agent aiming at secondary granule formation would have to act through.