Clonal rearrangement and expression of the T cell receptor beta gene and involvement of the breakpoint cluster region in blast crisis of CGL

A case of lymphoid blast crisis of Ph1-positive CGL is described in which the blast cells had an immature T cell phenotype, clonal rearrangement and expression of the T cell receptor beta gene, and a rearrangement of the breakpoint cluster region (bcr) on chromosome 22. This case therefore provides definite evidence for transformation involving a common myeloid-T lineage progenitor, penetrance of the Ph1 molecular alteration into the T cell lineage, and clonal selection in blast crisis at the level of a committed T lineage precursor.     

Age-related deficiency of the synthesis of platelet activating factor by leukocytes from Zellweger patients

Ca2+-ionophore A23187-induced synthesis of the alkoxyether lipid platelet activating factor (PAF) by leukocytes from Zellweger patients was undetectable in two patients studied at 3 and 4 weeks of age, reduced in a third patient studied at 2 months of age, and in the low normal range in four patients studied between 4 months and 5 years of age. We have previously reported that plasmalogen-type phosphatidylethanolamine (PE) levels of erythrocytes are reduced in Zellweger patients up to 20 weeks of age, but normal in older patients. These levels were reduced in the three patients with abnormal PAF synthesis, and normal in the other four patients. The results suggest a close relationship between the age of the patients at sampling, and both the A23187-induced capacity of leukocytes to synthesize PAF and the plasmalogen PE levels in their erythrocytes.     

Establishment of two new myeloma cell lines from bilateral pleural effusions: evidence for sequential in vivo clonal change

Two new human myeloma cell lines have been established from a 36-year- old woman with refractory IgG kappa multiple myeloma in whom bilateral malignant pleural effusions developed. The malignant plasma cells from each effusion were set up in a liquid culture using an L-15 medium containing catalase, glutathione, selenous acid, ascorbic acid, insulin, transferrin, additional glutamine hydrocortisone, and 2- mercaptoethanol and designated as M-3 medium. Two IgG kappa cell lines, LB -831 and LB-832, were established and proved to be Epstein-Barr virus negative using the internal repeat sequence DNA probe. Characteristic plasma cell morphology was evident by light and electron microscopy. Immunotyping revealed an IgG kappa , B1+, B2-, Ia (HLA- DR)+, CALLA+ phenotype for each cell line as well as for the original pleural fluid and bone marrow myeloma cells. The supernatants also contained IgG kappa, beta 2 microglobulin, and large amounts of osteoclast-activating factor (indicating bone-resorbing activity). Cytogenetic analysis of the LB-831 cell line revealed a nearly triploid highly abnormal karyotype with numerous clonal chromosomal abnormalities involving chromosomes 1, 3, 5, 7, 13, and 15; several structurally abnormal marker chromosomes; and a putative homogeneously staining region on chromosome 7p at band p22. Analysis of the LB-832 cell line revealed several additional clonal abnormalities. These additional cytogenetic changes suggest that in vivo sequential clonal evolution occurred in this patient. Therefore, two new but related cell lines have been established, which should prove useful for further biological studies.     

Immunotherapy in biliary tract cancers: Current evidence and future perspectives

Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder tumors. These are aggressive tumors and chemotherapy is still the main treatment for advanced-stage disease and most of these cases have a poor overall survival. Strategies are aimed at treatments with better outcomes and less toxicity which makes immunotherapy an area of ​​significant importance. Recent Food and Drug Administration approvals of immune checkpoint inhibitors (ICI) for agnostic tumors based on biomarkers such as microsatellite instability-high and tumor mutation burden-high are important steps in the treatment of patients with advanced bile duct tumors. Despite limited responses with isolated checkpoint inhibitors in later lines of systemic treatment in advanced disease, drug combination strategies have been demonstrating encouraging results to enhance ICI efficacy.