Complement or insult: the emerging link between complement cascade deficiencies and pathology of myeloid malignancies.

The complement cascade is an ancient and highly conserved arm of the immune system. The accumulating evidence highlights elevated activity of the complement cascade in cancer microenvironment and emphasizes its effects on the immune, cancer, and cancer stroma cells, pointing to a role in inflammation-mediated etiology of neoplasms. The role the cascade plays in development, progression, and relapse of solid tumors is increasingly recognized, however its role in hematological malignancies, especially those of myeloid origin, has not been thoroughly assessed and remains obscure.

Transcriptomics of acute myeloid leukaemia core bone marrow biopsies reveals distinct therapy response-specific osteo-mesenchymal profiles.

While the bone marrow (BM) microenvironment is significantly remodelled in acute myeloid leukaemia (AML), molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma. We assessed the effect of anthracycline- and cytarabine-based induction chemotherapy on both haematopoietic and non-haematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis. We compared matched human core BM biopsies at diagnosis and 2 weeks after cytarabine- and anthracycline-based induction therapy in responders (<5% blasts present after treatment) and non-responders (≥5% blasts present after treatment).

Nonhuman IAPP Variants Inhibit Human IAPP Aggregation.

Aim: To identify naturally occurring variants of IAPP capable of inhibiting the aggregation of human IAPP and protecting living cells from the toxic effects of human IAPP.

Background: The loss of insulin-producing β-cells and the overall progression of type 2 diabetes appears to be linked to the formation of toxic human IAPP (hIAPP, Islet Amyloid Polypeptide, amylin) amyloid in the pancreas. Inhibiting the initial aggregation of hIAPP has the potential to slow, if not stop entirely, the loss of β-cells and halt the progression of the disease.

Amyloidogenicity of naturally occurring full-length animal IAPP variants.

The aggregation of the 37-amino acid polypeptide human islet amyloid polypeptide (hIAPP), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of human pancreatic β-islet cells in type 2 diabetes. hIAPP is considered to be one of the most amyloidogenic proteins known. The quick aggregation of hIAPP leads to the formation of toxic species, such as oligomers and fibers, that damage mammalian cells (both human and rat pancreatic cells).