Posted by rob on February 23, 2005 under Uncategorized | 
Cytogenetic testing for therapeutic indication in cancer.
Mundle S, Noskina Y
Expert Rev Mol Diagn. 2005 Jan ; 5(1): 23-9
The association of cytogenetic abnormalities with cancer is well established. However, due to the historic lack of specific insight into the functional role of these anomalies, they have mostly served as diagnostic and/or prognostic indicators. Recent developments in chronic myelogenous leukemia and breast cancer have raised hopes for specific cytogenetic alterations to serve as therapeutic targets. This article reviews the aid provided by molecular diagnostics in these exciting developments in the cancer arena.
Cytogenetic testing for therapeutic indication in cancer.
Posted by rob on under Uncategorized |
Mastocytosis: pathology, genetics, and current options for therapy.
Valent P, Akin C, Sperr WR, Mayerhofer M, Födinger M, Fritsche-Polanz R, Sotlar K, Escribano L, Arock M, Horny HP, Metcalfe DD
Leuk Lymphoma. 2005 Jan ; 46(1): 35-48
Mast cell disorders are defined by an abnormal accumulation of tissue mast cells (MCs) in one or more organ systems. Symptoms in mastocytosis result from MC-derived mediators and, less frequently, from destructive infiltration of MCs. Cutaneous mastocytosis (CM) is a benign disease of the skin and may regress spontaneously. Systemic mastocytosis (SM) is a persistent disease in which a somatic c-kit mutation at codon 816 is usually detectable in MCs and their progenitors. The clinical course in these patients is variable ranging from asymptomatic for years to highly aggressive and rapidly devastating. The WHO discriminates five categories of SM: indolent SM (ISM), aggressive SM (ASM), SM with associated clonal hematological non-MC-lineage disease (AHNMD), and mast cell leukemia (MCL). The c-kit mutation D816V is quite common and may be found in all SM-categories. In SM-AHNMD, additional genetic abnormalities have been reported, whereas no additional defects are yet known for ASM or MCL. Patients with ISM and CM are treated with “mediator-targeting” drugs, whereas patients with ASM or MCL are candidates for cytoreductive therapy. The use of “Kit-targeting” tyrosine kinase inhibitors such as STI571 (Imatinib, Gleevec), has also been suggested. However, the D816V mutation of c-kit is associated with relative resistance against STI571. Therefore, these patients require alternative targeted drugs or new drug-combinations. In patients with SM-AHNMD, separate treatment plans for the SM-component and the AHNMD should be established. Examples include the use of STI571 in patients with SM plus hypereosinophilic syndrome (SM-HES) and the FIPL1/PDGFRA fusion gene target, or chemotherapy for eradication of AML in patients with SM-AML.
Mastocytosis: pathology, genetics, and current options for therapy.
Posted by rob on under Uncategorized |
In the Deep South we have started getting the first flowers of Spring a month earlier than last year.
Posted by rob on under Uncategorized |
Vaccine development for chronic myelogenous leukaemia.
Wong KK, Chatterjee S
Lancet. 2005 Feb 19; 365(9460): 631-2
Vaccine development for chronic myelogenous leukaemia.
Posted by rob on under Uncategorized |
Clonal evolution with inv(11)(p15q22) and NUP98/DDX10 fusion gene in imatinib-resistant chronic myelogenous leukemia.
Yamamoto M, Kakihana K, Kurosu T, Murakami N, Miura O
Cancer Genet Cytogenet. 2005 Mar ; 157(2): 104-8
The BCR/ABL tyrosine kinase inhibitor imatinib has shown remarkable efficacy in treating patients with chronic myelogenous leukemia (CML). In a small portion of patients treated with imatinib, however, the disease may progress to advanced stages, frequently accompanied by cytogenetic clonal evolution with the appearance of additional chromosomal aberrations besides the Philadelphia chromosome. Here we report the appearance of an inv(11)(p15q22) as a clonal evolution in a CML patient undergoing treatment with imatinib. Leukemic cells from the patient were found to express the fusion transcript of NUP98 and DDX10, which is in accordance with previously reported cases of de novo or therapy-related acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(p15q22). Although the patient showed resistance to imatinib with the disease rapidly progressing to blast crisis, sequence analysis failed to reveal any mutation in the kinase domain of BCR/ABL that would explain the imatinib resistance. Furthermore, ex vivo treatment of leukemic cells with imatinib significantly reduced tyrosine phosphorylation of CrkL, a target of the BCR/ABL kinase. These observations raise a possibility that the NUP98/DDX10 fusion might be involved in imatinib resistance as well as in acute transformation of CML.
Clonal evolution with inv(11)(p15q22) and NUP98/DDX10 fusion gene in imatinib-resistant chronic myelogenous leukemia.
