No abstract

1971; Slapak et al., 1971) and our own findings make it possible to construct a probable sequence of events in the hyperacute rejection process. The first change appears to be damage to the capillary endothelium presumably by an antibody antigen complex with subsequent binding of complement. This is followed by platelets adhering to the damaged endothelium and subsequent aggregation in the glomerular and peritubular capillaries. Substances released from these damaged platelets could result in the intense vasoconstriction, which together with the platelet plugs themselves could cause acute haemostasis and immediate rejection. Thrombosis is probably a later and secondary change.The action of heparin in prolonging graft survival is probably due to its direct effect on the platelets. This is consistent with our findings of a reduced fall in the platelet count in the heparintreated dogs. Linn et al. (1971) suggested that substances released by the breakdown of complement contribute to the vasoconstriction during acute rejection. For this reason we established that our heparin preparation was free from anticomplementary activity. Modification of the rejection process with aspirin or cyproheptadine hydrochloride (Periactin) could also be explained by their antagonism to platelet aggregation (O'Brien, 1968; Burrows et al., 1970).

No abstract

E-cadherin gene is often termed a “metastasis suppressor” gene because the E-cadherin protein can suppress tumor cell invasion and metastasis. Inactivation of the E-cadherin gene occurs in undifferentiated solid tumors by both genetic and epigenetic mechanisms; however, the role of E-cadherin in hematologic malignancies is only now being recognized. E-cadherin expression is essential for erythroblast and normoblast maturation, yet expression is reduced or absent in leukemic blast cells. This study examined the messenger RNA (mRNA) and protein expression of the E-cadherin gene in bone marrow and blood samples from normal donors and patients with leukemia. We found that all normal donor samples expressed E-cadherin mRNA, whereas both samples of acute myelogenous leukemia and chronic lymphocytic leukemia had a significant reduction or absence of expression. However, normal blast counterparts expressed only a low level of E-cadherin surface protein. Sodium bisulphite genomic sequencing was used to fully characterize the methylation patterns of the CpG island associated with the E-cadherin gene promoter in those samples with matched DNA. All of the normal control samples were essentially unmethylated; however, 14 of 18 (78%) of the leukemia samples had abnormal hypermethylation of the E-cadherin CpG island. In fact both alleles of the E-cadherin gene were often hypermethylated. We conclude the E-cadherin gene is a common target for hypermethylation in hematologic malignancies.