Abstract: Transformation of myeloproliferative disorders (MPDs) to acute leukemia is an evitable event that represents a stumbling block in the management of patients. The Janus Kinase-2 JAK2V617F mutation of MDP does not clarify the phenotypic variability observed in this disorder. But, a mutations in Ten-eleven-translocation-2 (TET2), a putative tumor suppressor gene, was recently implicated in MPDs and other hematologic malignancies. TET-2 is believed to play a role in leukemic transformation. This study aimed to determine the frequency of L1721W polymorphism in TET2 gene in a cohort of Sudanese patients with MPDs. Following informed consent, 25 (25/50, 50%) patients with polycythemia rubra vera (PRV), thirteen patients (13/50, 26%) with essential thrombocythemia (ET), eleven patients (11/50, 22%) with chronic myeloid leukemia (CML), and one patient (1/50, 2%) with primary myelofibrosis (PMF) were enrolled. None of the patients was in the transformation phase. Patients were diagnosed based on clinical picture, hematological parameters and JAK2V617F and BCR_ABL molecular aberrations. JAK2V617F was detected in Ph-negative-MPDs cases as (24/25, 96%) in PRV, (10/13, 76%) in ET, and (1/1, 100%) in PMF. BCR_ABL fusion was detected in all (11/11, 100%) cases of CML. DNA was extracted using the guanidine chloride method, followed by (PCR-RFLP) analysis. Only one patient showed the presence of L1721W polymorphism of the TET2. It was inferred that the low frequency of this transformation within the study cohort [all in chronic phase] probably indicates that it plays a minor role in MPD pathogenesis, while its role in blast transformation needs further studies in MPD patients.Abstract: Transformation of myeloproliferative disorders (MPDs) to acute leukemia is an evitable event that represents a stumbling block in the management of patients. The Janus Kinase-2 JAK2V617F mutation of MDP does not clarify the phenotypic variability observed in this disorder. But, a mutations in Ten-eleven-translocation-2 (TET2), a putative tumor supp...Show More
Abstract: The numbers of CD133+ and CD31+ lymphocytes and those in the G2-M phases in the total fraction of circulating lymphocytes from patients with fatal liver cirrhosis and advanced lung cancer were investigated by flow cytometry during a long period of conventional treatment with OLT or palliative surgery followed by myelosuppressive chemotherapy. The relationships of specific reproductive activity, sRA (G2-M/CD133+), and the number of committed liver α-fetoprotein-positive (AFP+) cells with the rate of patient deaths, characterized by exponential approximation survival curves for both diseases, were investigated. Subnormal sRA in patients after OLT and excessive sRA in LC patients above a healthy level were associated with higher death rates and lower survival, coinciding with strong immunosuppression caused by anti-rejection and anti-cancer therapies. These findings may be explained by morphogenesis (feeding) activity of circulating lymphocytes targeted toward both normal and malignant tissues rather than in terms of cellular immunity. The sRA changes may be a useful indicator for monitoring the potential for engraftment or tumor growth.Abstract: The numbers of CD133+ and CD31+ lymphocytes and those in the G2-M phases in the total fraction of circulating lymphocytes from patients with fatal liver cirrhosis and advanced lung cancer were investigated by flow cytometry during a long period of conventional treatment with OLT or palliative surgery followed by myelosuppressive chemotherapy. The r...Show More
