Sequential emergence of ABL-kinase mutations with loss of unmutated BCR-ABL allele during targeted therapies of CML.
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Aged↗
Biomedical subjects
Lydia Roy
Publications and source records attributed to Lydia Roy.
Survival advantage from imatinib compared with the combination interferon-alpha plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials.
In the multinational IRIS study comparing imatinib with interferon plus cytarabine (IFN/Ara-C) in patients with newly diagnosed chronic-phase chronic myelogenous leukemia (CP CML), imatinib demonstrated significantly higher rates of complete cytogenetic responses (CCyRs) and improved progression-free survival (PFS). However, because of a high early crossover rate to imatinib, survival benefit was not assessable. Here, we report the result of a study comparing long-term outcome of patients included in 2 prospective randomized trials: 551 patients assigned to imatinib in the IRIS trial from 2000 to 2001 and 325 patients who received the combination IFN/Ara-C in the CML91 trial between 1991 and 1996 before imatinib was available. With a follow-up of 42 months for both groups of patients, estimated CCyR, survival free of transformation, and overall survival were significantly higher with imatinib compared with IFN/Ara-C (P < .001, P = .004, and P < .001, respectively). Improved overall survival was also confirmed within different Sokal prognostic risk groups. Of interest, among all patients who achieved major cytogenetic response or CCyR at 12 months, the survival rate was similar irrespective of their treatment. In conclusion, within the limitation of this historical comparison, there is a survival advantage from first-line therapy with imatinib over IFN/Ara-C.
Adult↗
Interferon therapy in chronic myelogenous leukemia.
Interferon (IFN)-alpha, the molecule used in the treatment of chronic myelogenous leukemia and initially prepared from human leucocytes,is now produced essentially by recombinant techniques. Polyethylene glycol (PEG) modifications of proteins could be more effective than the regular molecules; thus, pegylated IFNs more recently have been tested in chronic myelogenous leukemia. PEG modification of proteins reduces sensitivity to proteolysis. Moreover,administration of pegylated IFNs results in less antigenicity and immunogenicity, and prolongation of their plasma half-life has been assessed by pharmacokinetic studies. It is assumed, therefore, that this compound could be more effective and better tolerated. Given the results recently obtained with imatinib, however, whether IFN-alpha will still have a therapeutic role is questionable.
Antineoplastic Combined Chemotherapy Protocols↗
High dose chemotherapy in light chain or light and heavy chain deposition disease.
BACKGROUND: Conventional chemotherapy for myeloma yield unsatisfactory results in light and/or heavy chain deposition disease [(H)CDD] Because of the well-established dose-response effect of high dose melphalan in multiple myeloma, aiming to dramatically reduce the pathogenic monoclonal immunoglobulin (MIg) level, high dose therapy is a tempting alternative approach. METHODS: We treated 11 young patients with L(H)CDD by high dose therapy with the support of autologous blood stem cell transplantation. All had renal symptoms, including four who required dialysis and seven who had various, mainly cardiac, extrarenal manifestations. RESULTS: No toxic deaths occurred. A decrease in the MIg level was observed in eight patients, with complete disappearance from serum and urine in six cases. Improvement in manifestations related to MIg deposits were observed in six patients, including renal, cardiac, and hepatic responses in 4/11, 4/4, and 2/2 cases, respectively. Histologic regression of MIg deposits was documented in cardiac, hepatic, and skin biopsies. In contrast, examination of the kidney still showed light chain deposits in one patient who had renal transplantation 3 years after high dose therapy, at a time when he was in persisting remission. Within a median follow-up of 51 months, three patients were retreated because of multiple myeloma relapse, of whom one died and one required hemodialysis, and renal function secondarily deteriorated in a patient who had resistant multiple myeloma. Otherwise, no manifestations related to MIg deposits occurred or recurred in any patient. CONCLUSION: Present results of this retrospective study argue in favor of a benefit of high dose therapy with stem cell support in young patients with L(H)CDD.
Adult↗
Megakaryocyte polyploidization is associated with a functional gene amplification.
It is believed that polyploidy induces an orchestrated increase in gene expression. To know whether all alleles remain functional during megakaryocyte polyploidization, we used a well-established fluorescence in situ hybridization technique which allows one to simultaneously detect pre-mRNAs and assess ploidy level in a single cell. All alleles of GPIIb, GPIIIa, VWF, beta-actin, hsp70, c-mpl, Fli-1, and FOG-1 genes are transcriptionally active in megakaryocytes from 4N to 32N. All X chromosomes in male cells are transcriptionally active but only half of them are transcriptionally active in female megakaryocytes, as revealed by the transcriptional activity of the GATA-1 gene. Nuclear untranslated XIST RNA accumulates on the inactivated X chromosomes, indicating that they are subjected to a normal inactivation process. Altogether, our results demonstrate that megakaryocyte polyploidization results in a functional gene amplification whose likely function is an increase in protein synthesis parallel with cell enlargement.
Alleles↗
PRINS, the other in situ DNA labeling method useful in cellular biology.
PRINS has proven to be an attractive alternative to FISH for in situ DNA labeling. PRINS is specific, simple, and rapid. We review some applications of PRINS involving primers specific for telomeric, human Alu, and centromeric alpha-satellite sequences. Bicolor labeling, PRINS-FISH, or PRINS-immunofluorescent combinations have been developed to enable investigations in numerous applications.
Animals↗