BCR-ABL fusion oncogene originates from the reciprocal translocation of chromosome 9 and 22 t(9;22) (q34;q11). It translates a chimeric protein, p210, characterized by constitutive activation of its tyrosine kinase, w...BCR-ABL fusion oncogene originates from the reciprocal translocation of chromosome 9 and 22 t(9;22) (q34;q11). It translates a chimeric protein, p210, characterized by constitutive activation of its tyrosine kinase, which triggers leukemogenic pathways resulting in onset of chronic myeloid leukemia (CML). In CML, the classic fusion is b2a2 or b3a2 fusing exon 13 (b2) or exon 14 (b3) of BCR to exon 2 (a2) of ABL. The type of bcr/abl transcripts may be associated with different prognosis and hence useful in therapeutic plan. This study was conducted to calculate the frequency of these splice variants as the frequencies of different fusion oncogenes associated with leukaemia can vary in different geographical regions due to interplay of genetic variation in different ethnic populations, diverse environmental factors and living style. A very sensitive nested RT-PCR was established to detect BCR-ABL splice variants in CML. Sensitivity of RT-PCR assay was of the order of 10–6. Thirty CML patients were subjected to BCR-ABL analysis. Out of 30 Pakistani patients, 19 (64%) expressed b3a2 while 11 (36%) expressed b2a2 transcript. This shows that BCR-ABL splice variants differ in their frequencies which may have an effect on biology and implications for prognosis and management of BCR-ABL positive Leukemias.展开更多
Background: Thioacetamide (TAA) has been used extensively in the development of suitable animal models of acute and chronic liver injury employing various doses, times and routes of its administration, particularly in...Background: Thioacetamide (TAA) has been used extensively in the development of suitable animal models of acute and chronic liver injury employing various doses, times and routes of its administration, particularly in drinking water due to its resemblance with human liver fibrosis and cirrhosis. The aim of this study was to investigate and compare hematological alteration during the acute and chronic liver inflammation. Methods: Acute Liver inflammation was induced in Wistar rats via intraperitoneal injection of thioacetamide and the animals were sacrificed 12 h after the TAA administration. Induction of chronic liver inflammation was performed by continuous administration of TAA in the drinking water (200 mg/L) during 18 weeks of experiment. After that all animals were sacrificed and Blood samples were collected for further analysis. Results: Single intra peritoneal injection of TAA (300 mg/kg B.W.) induced an acute condition with hematological changes including leukocytosis with marked neutrophilia (P = 0.0429), lymphopenia, thrombocytosis as well as increased hemoglobin concentration (P 0.05) and decline of erythrocytic count (P = 0.0009). Eighteen weeks of uninterrupted supply of TAA (200 mg/L) in drinking water lead to chronic inflammation and the hematological alterations were leucopenia (P = 0.0197) accompanied with neutropenia and thrombocytopenia. Increase in RBCs (P = 0.0073) and Hb contents was also observed with a decline of red cell indices. Conclusion: Taken together these findings we can conclude that the animals respond differently under acute and chronic inflammatory condition with TAA administration. Leukocytosis with marked neutrophilia, thrombocytosis as well as increased hemoglobin concentration and decline of erythrocytic count were observed in acute while leucopenia accompanied with neutropenia and thrombocytopenia and increase in RBCs, Hb and Hct was also observed with a decline of other red cell indices during chronic phase.展开更多
文摘BCR-ABL fusion oncogene originates from the reciprocal translocation of chromosome 9 and 22 t(9;22) (q34;q11). It translates a chimeric protein, p210, characterized by constitutive activation of its tyrosine kinase, which triggers leukemogenic pathways resulting in onset of chronic myeloid leukemia (CML). In CML, the classic fusion is b2a2 or b3a2 fusing exon 13 (b2) or exon 14 (b3) of BCR to exon 2 (a2) of ABL. The type of bcr/abl transcripts may be associated with different prognosis and hence useful in therapeutic plan. This study was conducted to calculate the frequency of these splice variants as the frequencies of different fusion oncogenes associated with leukaemia can vary in different geographical regions due to interplay of genetic variation in different ethnic populations, diverse environmental factors and living style. A very sensitive nested RT-PCR was established to detect BCR-ABL splice variants in CML. Sensitivity of RT-PCR assay was of the order of 10–6. Thirty CML patients were subjected to BCR-ABL analysis. Out of 30 Pakistani patients, 19 (64%) expressed b3a2 while 11 (36%) expressed b2a2 transcript. This shows that BCR-ABL splice variants differ in their frequencies which may have an effect on biology and implications for prognosis and management of BCR-ABL positive Leukemias.
文摘Background: Thioacetamide (TAA) has been used extensively in the development of suitable animal models of acute and chronic liver injury employing various doses, times and routes of its administration, particularly in drinking water due to its resemblance with human liver fibrosis and cirrhosis. The aim of this study was to investigate and compare hematological alteration during the acute and chronic liver inflammation. Methods: Acute Liver inflammation was induced in Wistar rats via intraperitoneal injection of thioacetamide and the animals were sacrificed 12 h after the TAA administration. Induction of chronic liver inflammation was performed by continuous administration of TAA in the drinking water (200 mg/L) during 18 weeks of experiment. After that all animals were sacrificed and Blood samples were collected for further analysis. Results: Single intra peritoneal injection of TAA (300 mg/kg B.W.) induced an acute condition with hematological changes including leukocytosis with marked neutrophilia (P = 0.0429), lymphopenia, thrombocytosis as well as increased hemoglobin concentration (P 0.05) and decline of erythrocytic count (P = 0.0009). Eighteen weeks of uninterrupted supply of TAA (200 mg/L) in drinking water lead to chronic inflammation and the hematological alterations were leucopenia (P = 0.0197) accompanied with neutropenia and thrombocytopenia. Increase in RBCs (P = 0.0073) and Hb contents was also observed with a decline of red cell indices. Conclusion: Taken together these findings we can conclude that the animals respond differently under acute and chronic inflammatory condition with TAA administration. Leukocytosis with marked neutrophilia, thrombocytosis as well as increased hemoglobin concentration and decline of erythrocytic count were observed in acute while leucopenia accompanied with neutropenia and thrombocytopenia and increase in RBCs, Hb and Hct was also observed with a decline of other red cell indices during chronic phase.
