Posted by rob on January 27, 2006 under Uncategorized | 
Recently, large deletions adjacent to the Philadelphia (Ph) translocation breakpoint on the derivative chromosome 9 have been reported to be found in a substantial number of patients with chronic myelogenous leukemia (CML). The existence of der(9) deletion is reported as a powerful indicator of a poor prognosis. So far, der(9) deletion is considered to be generated when the Ph translocation occurs, because when der(9) deletion is found, it is detected in all the Ph-positive (Ph+) cells of a particular CML patient. On FISH examination of 47 Vietnamese CML patients, we found 11 patients carrying der(9) deletion. Among these, two patients harbored Ph+ metaphase cells with der(9) deletion and also Ph+ cells without it. In CML patients with der(9) deletion, reportedly no ABL/BCR transcript is detected. In these two patients, the proportion of Ph+ cells without der(9) deletion was much smaller than that of the cells with der(9) deletion. Nevertheless, we detected a ABL/BCR (1b-b4) transcript in the two patients. This is further evidence for the existence of Ph+ cells without der(9) deletion. It is possible that in some CML patients, der(9) deletion is generated in the progression of the disease.
Coexistence of Philadelphia chromosome positive cells with and without der(9) deletion in a patient with chronic myelogenous leukemia.
Posted by rob on under Uncategorized |
Imatinib mesylate has become the gold standard front-line treatment of chronic myelogenous leukemia through its ability to inhibit ABL tyrosyne kinase. Resistance to this inhibition may occur. We investigated the role of the K247R polymorphism in persistent sensitivity.
The role of the K247R substitution in the ABL tyrosine kinase domain in sensitivity to imatinib.
Posted by rob on under Uncategorized |
Yang H,
Eaves C,
de Lima M,
Lee MS,
Champlin RE,
McMannis JD,
Robinson SN,
Niu T,
Decker WK,
Xing D,
Ng J,
Li S,
Yao X,
Eaves AC,
Jones R,
Andersson BS,
Shpall EJ
Imatinib-refractory chronic myelogenous leukemia (CML) patients can experience long-term disease-free survival with myeloablative therapy and allogeneic hematopoietic cell transplantation; however, associated complications carry a significant risk of mortality. Transplantation of autologous hematopoietic cells has a reduced risk of complications, but residual tumor cells in the autograft may contribute to relapse. Development of methods for purging tumor cells that do not compromise the engraftment potential of the normal hematopoietic cells in the autograft has been a long-standing goal. Since primitive CML cells differentiate more rapidly in vitro than their normal counterparts and are also preferentially killed by mafosfamide and imatinib, we examined the purging effectiveness on CD34(+) CML cells using a strategy that combines a brief exposure to imatinib (0.5-1.0 muM for 72 h) and then mafosfamide (30-90 mug/ml for 30 min) followed by 2 weeks in culture with cytokines (100 ng/ml each of stem cell factor, granulocyte colony-stimulating factor and thrombopoietin). Treatment with 1.0 muM imatinib, 60 mug/ml mafosfamide and 14 days of culture with cytokines eliminated BCR-ABL(+) cells from chronic phase CML patient aphereses, while preserving normal progenitors. This novel purging strategy may offer a new approach to improving the effectiveness of autologous transplantation in imatinib-refractory CML patients.Bone Marrow Transplantation advance online publication, 23 January 2006; doi:10.1038/sj.bmt.1705284.
A novel triple purge strategy for eliminating chronic myelogenous leukemia (CML) cells from autografts.
