Treatments Principles in Malignant Homeopathies

Aim of this study is to present the latest researches in the field of molecular medicine, in terms of treatments in malignant hemopathies, emerged from the P53 gene deletion in human lymphoma genome. Method: In recent years proved that the best techniques in the investigation of malignant lymphocytes are the Flow Cytometry, Elisa, ICT and Fluorescence in situ hybridization (FISH). This method is used as an alternative to chromosomal banding, a conventional application in molecular medicine. Discussion: Recent, endogenous somatic gene therapy research is a basic of trial clinical and therapeutic trial. The DNA is used to treat a disease arising as a result of mutations in chromosomal regions. In the past few years, this method has been included in the treatment of CLL, acute lymphocytic leukemia, [ALL], or multiple myeloma [MM]. Conclusion: The frequencies of P53 gene mutations and deletion in CLL can be categorized as individual biomarkers in proteomic and genomic profile for this type of leukemia that can be implemented in targeted patient treatment of personalized medicine.

P53 Abnormality and Prognostic Impact In Leukemia Patients with Complex Chromosomal Abnormalities

Abstract 4847 Objective: To investigate the prevalence of p53 gene deletion in leukemia patients with complex chromosome abnormalities (CCA) and their relative prognostic impact. Methods: The chromosome abnormalities in acute leukemia cases with R banding method, karyotype is named according to international nomenclature ISCN 2005. Interphase fluorescence in situ hybridization (I-FISH) determinations were performed to detect the percentage and frequency of p53 gene deletion in 38 leukemia patients with CCA and 24 patients without CCA. The rate of complete remission (CR) and median survival time (MST) were observed between the two groups in patients with CCA or without CCA. Results: (1) Complex karyotype abnormality in the leukemia patients involved in almost all of chromosomes, especially chromosome 17, chromosome 5, and chromosome 7. And the reduction of chromosome number was more common than the increase. (2) The threshold of two green and one red (2G1R) was 7%, the threshold of one green and one red (1G1R) was 4.9%. (3) The percentage of p53 gene deletion was 44.74% in CCA group and 4.16% in non-CCA group (p<0.0001). (4) p53 gene deletions were found in 9 of 10 cases with chromosome 17 abnormalities. The percentage of p53 gene deletion was achieved in 90%. (5) The CR rate was 57.14% and the MST was 31 months in patients with non-CCA compared to 11.76% CR rate and 2 months MST in patients with CCA (p<0.0001). Conclusion: The deletion of p53 gene appears to be associated with complex chromosome abnormalities and may play an important role in the prognosis of patients with leukemia Disclosures: No relevant conflicts of interest to declare.

2-phenylacetylenesulfonamide (PAS) induces p53-independent apoptotic killing of B-chronic lymphocytic leukemia (CLL) cells

We studied the actions of 2-phenylacetylenesulfonamide (PAS) on B-chronic lymphocytic leukemia (CLL) cells. PAS (5-20 μM) initiated apoptosis within 24 hours, with maximal death at 48 hours asassessed by morphology, cleavage of poly(ADP-ribose) polymerase (PARP), caspase 3 activation, and annexin V staining. PAS treatment induced Bax proapoptotic conformational change, Bax movement from the cytosol to the mitochondria, and cytochrome c release, indicating that PAS induced apoptosis via the mitochondrial pathway. PAS induced approximately 3-fold up-regulation of proapoptotic Noxa protein and mRNA levels. In addition, Noxa was found unexpectedly to be bound to Bcl-2 in PAS-treated cells. PAS treatment of CLL cells failed to up-regulate p53, suggesting that PAS induced apoptosis independently of p53. Furthermore, PAS induced apoptosis in CLL isolates with p53 gene deletion in more than 97% of cells. Normal B lymphocytes were as sensitive to PAS-induced Noxa up-regulation and apoptosis as were CLL cells. However, both T lymphocytes and bone marrow hematopoietic progenitor cells were relatively resistant to PAS. Our data suggest that PAS may represent a novel class of drug that induces apoptosis in CLL cells independently of p53 status by a mechanism involving Noxa up-regulation.