Monitoring plasma imatinib level to improve results of therapy of chronic myeloid leukosis

The achievement of early cytogenetic and molecular responses is the major objective of therapy and a main prerequisite for the favourable long-term outcome of the disease. The maintenance of dose intensity and management of adverse events are keys to successful treatment of chronic myeloid leukemia (CML) with imatinib. Therapeutic monitoring and testing the drug level in blood are the efficient tools for the treatment ofpatients with CML and can be usedfor analysis of treatment failure or suboptimal response to therapy, suspected noncompliance, drug interactions or unexpected adverse reactions.

TheMETGene Is a Common Integration Target in Avian Leukosis Virus Subgroup J-Induced Chicken Hemangiomas

ABSTRACTAvian leukosis virus subgroup J (ALV-J) is a simple retrovirus that can cause hemangiomas and myeloid tumors in chickens and is currently a major economic problem in Asia. Here we characterize ALV-J strain PDRC-59831, a newly studied U.S. isolate of ALV-J. Five-day-old chicken embryos were infected with this virus, and the chickens developed myeloid leukosis and hemangiomas within 2 months after hatching. To investigate the mechanism of pathogenesis, we employed high-throughput sequencing to analyze proviral integration sites in these tumors. We found expanded clones with integrations in theMETgene in two of the five hemangiomas studied. This integration locus was not seen in previous work characterizing ALV-J-induced myeloid leukosis.METis a known proto-oncogene that acts through a diverse set of signaling pathways and is involved in many neoplasms. We show that tumors harboringMETintegrations exhibit strong overexpression ofMETmRNA.IMPORTANCEThese data suggest that ALV-J induces oncogenesis by insertional mutagenesis, and integrations in theMEToncogene can drive the overexpression ofMETand contribute to the development of hemangiomas.

Identification of two novel multiple recombinant avian leukosis viruses in two different lines of layer chicken

Avian leukosis virus (ALV) is the most common oncogenetic retrovirus that emerges spontaneously as a result of recombination between exogenous viruses, exogenous viruses and endogenous viruses, and exogenous viruses and non-homologous cellular genes. In the present study, two natural recombinant avian leukosis viruses (rALVs) (LC110515-5 and LC110803-5) carrying a subgroup C gp85 gene, a subgroup E gp37 gene, and a subgroup J 3′UTR and 3′LTR were isolated from two different lines of layer flocks, Black-bone silky fowl (BSF) and commercial layer chicken, that suffered from myeloid leukosis. Although tumours were not observed in rALV-infected individual chickens, other non-neoplastic inflammatory lesions were evident. The two rALVs were cultured on DF-1 cells and identified by PCR, immunofluorescence assay and gene sequencing. The gp85 nucleotide sequence in the two isolates displayed a high identity (>95 %) with that of the gp85 gene in ALV-C, but the identity was less than 90 % with ALV-A/B/D/E and only 51 % with ALV-J. Phylogenetic analysis of the nucleotide and amino acid sequences confirmed that the two isolates were recombinant between ALV-C, ALV-E and ALV-J. Subgroup C ALV is rarely found in field cases. This report is the first to provide evidence that ALV-C has recombined with ALV-E and ALV-J in two different chicken lines. The source and characteristics of the two rALVs and ALV-C need to be further investigated.

Sequence analysis for the complete proviral genome of avian leukosis virus subgroup J associated with haemangiomas, leiomyosarcomas and myelomas in layer flocks

Avian leukosis virus subgroup J (ALV-J) can cause a variety of neoplasms, including mainly myeloid leukosis (myelocytomatosis) and nephromas. Other tumours, such as histiocytic sarcoma (HS), haemangiosarcoma and mesothelioma, may also develop. In a previous article we described a case in which myeloid leukosis, haemangiomas and leiomyosarcomas appeared simultaneously in a commercial layer flock with infection by ALV-J. The present research was completed to understand the molecular characteristics of the ALV-J strain that induced clinical myeloid leukosis, haemangiomas and leiomyosarcomas. Two strains of ALV-J (SDAU1001 and SDAU1002) were isolated and identified, and their full-length sequences were analysed. The complete genome nucleotide sequences of these two isolates were different in length, 7652 nt and 7636 nt, respectively. They shared 98.9% identity with each other, and 93.4% to 97.8% nucleotide identity to the reference ALV-J isolates. A 19-nucleotide repeat sequence was identified in the primer binding site (PBS) leader region of isolate SDAU1001. A base substitution mutation (base 15 C-T) in this insertion was identified. However, the identical insertion at the same site was not found in SDAU1002. Thegagandpolgenes of the two viruses were more conserved than theenvgene. One key deletion in the E element was a common feature of SDAU1001 and SDAU1002. SDAU1001 and SDAU1002, possibly recombinants of ALV-J and another avian retrovirus, may share the same ancestor. Co-infection by SDAU1001 and SDAU1002 isolates is a possible explanation why myeloid leukosis, haemangiomas, and leiomyosarcomas appeared simultaneously in the same commercial layer flock.

Pathology of spontaneous tumour lesions in pullets and adult chickens in commercial farms — Short communication

Twenty pullets and adult chickens, aged 100 to 403 days, from several commercial chicken farms were examined by gross and histopathology. Grossly, all chickens had white-greyish masses in the visceral organs with or without enlargement of the peripheral nerves. Histopathological examination revealed Marek’s disease (MD) lymphoma, lymphoid leukosis (LL) and myeloid leukosis (ML) in 14/20, 5/20 and 1/20 of the chickens, respectively. Lesions of the sciatic nerves in chickens diagnosed as having MD lymphoma were various. No neoplastic and/or inflammatory cells were noted in the peripheral nerves of chickens diagnosed as having LL and ML. These results indicated that MD lymphoma could also develop in older chickens; thus, microscopic examination is needed to identify MD in older chickens showing lymphocyte-derived tumours.