Background Arsenic trioxide (As2O3) has been identified as a very potent antiacute leukemic agent However its role in apoptosis needs to be elucidated As2O3 interferes with the proliferation and survival...Background Arsenic trioxide (As2O3) has been identified as a very potent antiacute leukemic agent However its role in apoptosis needs to be elucidated As2O3 interferes with the proliferation and survival of tumor cells via a variety of mechanisms Drugtarget interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by As2O3 This study dealt with As2O3-target interactions at the level of NM in chronic myelogenous leukemia cell line K562 by proteomics Methods K562 cells were cultured in MEM and treated with different concentrations of As2O3 The nuclear matrix proteins were analyzed by highresolution twodimensional gel electrophoresis and computerassisted image analysis Results As2O3 significantly inhibited the growth of chronic myelogenous leukemia cell line K562 at low concentrations While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots in the nuclear matrices were found characteristic for As2O3 treated cells Conclusions: As2O3 induces apoptosis in K562 cells in a dose and timedependent manner Our results demonstrated that for the detection of the onset of apoptosis, the alteration in the composition of nuclear matrix proteins was a more sensitive indicator than nucleosomal DNA fragmentation test These results indicated that As2O3 might be clinically useful in the treatment of chronic myelogenous leukemia. The changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for this展开更多
Human T-cell leukemia virus type 1(HTLV-1),the first human retrovirus discovered,is the etiological agent of adult-T-cell leukemia/lymphoma.The HTLV-1 encoded Tax protein is a potent oncoprotein that deregulates gene ...Human T-cell leukemia virus type 1(HTLV-1),the first human retrovirus discovered,is the etiological agent of adult-T-cell leukemia/lymphoma.The HTLV-1 encoded Tax protein is a potent oncoprotein that deregulates gene expression by constitutively activating nuclear factor-κB(NF-κB).Tax activation of NF-κB is critical for the immortalization and survival of HTLV-1-infected T cells.In this review,we summarize the present knowledge on mechanisms underlying Tax-mediated NF-κB activation,with an emphasis on post-translational modifications of Tax.展开更多
Objective: To study the frequency of interstitial 7q deletions in B-cell lymphoproliferative disorders (B-LPDs). Methods: Cases were collected from the clinical laboratory diagnosis database at USLabs/LabCorp over the...Objective: To study the frequency of interstitial 7q deletions in B-cell lymphoproliferative disorders (B-LPDs). Methods: Cases were collected from the clinical laboratory diagnosis database at USLabs/LabCorp over the past two years (2002 to 2004). Cases that showed deletions in the long arm of chromosome 7 were then reviewed. Interstitial deletions in the long arm of chromosome 7 were further investigated according to the indications for clinical laboratory studies and flow cytometry findings. The final clinical diagnosis for each case was obtained from the referring physician. Results: A total of 19 483 cases were included in this series. Eighty-five cases were observed to have either terminal or interstitial deletion in the long arm of chromosome 7. Of the 85 cases, 46 had interstitial deletions accounting for 54.1% of the 7q deletions combined. B-LPDs were found in 10 of the 46 cases, accounting for 21.7%. The B-LPDs associated with 7q interstitial deletions were diverse, including B-cell chronic lymphocytic leukemia (B-CLL) in five cases. The deleted region in the long arm of chromosome 7 in the 10 cases associated with B-LPDs was solely confined to the 7q22-q32 region. Conclusion: (1) The frequency of 7q interstitial deletions associated with B-LPDs is substantially high; (2) 7q interstitial deletions are not uncommon in B-CLL.展开更多
AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of p...AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of patients with hematological malignancies. All medical files of patients with malignant disease whose treatment was coordinated by the HematoOncology service of the Cayenne Hospital in French Guiana between the 1st of January 2010 and the 31 st of December 2012 were reviewed. Clinical data were extracted from the medical files and included: Demographic data, comorbidities, serological status for human immunodeficiency virus, human T-lymphotropic virus 1(HTLV1), hepatitis B virus and hepatitis C virusinfections, cytology and pathology diagnoses, disease extension, treatment, organization of disease management, and follow-up. The subgroup of patients with hematological malignancies and virus-related malignancies were reviewed. Cases involving patients with Kaposi sarcoma, and information on solid tumor occurrence in virus-infected patients in the whole patient population were included. Since the data were rendered anonymous, no informed consent was obtained from the patients for this retrospective analysis. Data were compiled using EXCEL® software, and the data presentation is descriptive only. The references search was guided by the nature of the data and discussion. RESULTS: In total, the clinical files of 594 patients(pts) were reviewed. Hematological malignancies were observed in 87 patients, and Kaposi sarcoma in 2 patients. In total, 70 patients had a viral infection, and 34 of these also had hematological malignancies. The hematological diagnoses were: Multiple myeloma in 27 pts, lymphoma(L) in 43 pts, myeloproliferative disorders in 17 pts and Kaposi sarcoma in two patients. The spectrum of non-Hodgkin lymphomas(NHL) was: Burkitt L(1 pt), follicular L(5 pts), chronic lymphocytic leukemia(5 pts), high-grade NHL(9 pts), mucosa-associated lymphoid tissue NHL(4 pts), T-cell lymphoma(4 pts), Adult T-cell lymphoma-leukemia(ATL)/lymphoma/leukemia(12 pts); three patients had Hodgkin disease. The spectrum of myeloproliferative diseases was: Chronic myelogenous leukemia(8 pts), thrombocytemia(5 pts) and acute leukemia(4 pts). There were no polycythemia vera, myelosclerosis, and myelodysplastic diseases. This appears to be due to bias in the recruitment process. The most important observations were: The specificity of HTLV1- related ATL malignancies, and the high incidence of virus infections in patients with hematological malignancies. Further, we noted several limitations regarding the treatment and organization of disease management. These were not related to the health care organization, but were due to a lack of board-certified hematooncology specialists, a lack of access to diagnostic tools(e.g., cytogenetic and molecular diagnosis, imaging techniques), the unavailability of radiotherapy, and the physical distance from mainland France. Yet the geography and cultures of the country also contributed to the encountered difficulties. These same limitations are seen in tropical countries with low and intermediate household incomes, but they are amplified by economic, social, and cultural issues. Thus, there is often little access to diagnostic procedures, adequate clinical management, and an unavailability of suitable medical treatments. Programs have been developed to establish centers of excellence, training in pathology diagnosis, and to provide free access to treatment.CONCLUSION: Management of hematological malignancies in tropical areas requires particular skills regarding specific features of these diseases and in terms of the affected populations, as well as solid public health policies.展开更多
文摘Background Arsenic trioxide (As2O3) has been identified as a very potent antiacute leukemic agent However its role in apoptosis needs to be elucidated As2O3 interferes with the proliferation and survival of tumor cells via a variety of mechanisms Drugtarget interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by As2O3 This study dealt with As2O3-target interactions at the level of NM in chronic myelogenous leukemia cell line K562 by proteomics Methods K562 cells were cultured in MEM and treated with different concentrations of As2O3 The nuclear matrix proteins were analyzed by highresolution twodimensional gel electrophoresis and computerassisted image analysis Results As2O3 significantly inhibited the growth of chronic myelogenous leukemia cell line K562 at low concentrations While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots in the nuclear matrices were found characteristic for As2O3 treated cells Conclusions: As2O3 induces apoptosis in K562 cells in a dose and timedependent manner Our results demonstrated that for the detection of the onset of apoptosis, the alteration in the composition of nuclear matrix proteins was a more sensitive indicator than nucleosomal DNA fragmentation test These results indicated that As2O3 might be clinically useful in the treatment of chronic myelogenous leukemia. The changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for this
基金Supported by Grants from the United States Public Health Service/National Institutes of Health,No.RO1CA135362,RO1GM083143 and PO1CA128115
文摘Human T-cell leukemia virus type 1(HTLV-1),the first human retrovirus discovered,is the etiological agent of adult-T-cell leukemia/lymphoma.The HTLV-1 encoded Tax protein is a potent oncoprotein that deregulates gene expression by constitutively activating nuclear factor-κB(NF-κB).Tax activation of NF-κB is critical for the immortalization and survival of HTLV-1-infected T cells.In this review,we summarize the present knowledge on mechanisms underlying Tax-mediated NF-κB activation,with an emphasis on post-translational modifications of Tax.
文摘Objective: To study the frequency of interstitial 7q deletions in B-cell lymphoproliferative disorders (B-LPDs). Methods: Cases were collected from the clinical laboratory diagnosis database at USLabs/LabCorp over the past two years (2002 to 2004). Cases that showed deletions in the long arm of chromosome 7 were then reviewed. Interstitial deletions in the long arm of chromosome 7 were further investigated according to the indications for clinical laboratory studies and flow cytometry findings. The final clinical diagnosis for each case was obtained from the referring physician. Results: A total of 19 483 cases were included in this series. Eighty-five cases were observed to have either terminal or interstitial deletion in the long arm of chromosome 7. Of the 85 cases, 46 had interstitial deletions accounting for 54.1% of the 7q deletions combined. B-LPDs were found in 10 of the 46 cases, accounting for 21.7%. The B-LPDs associated with 7q interstitial deletions were diverse, including B-cell chronic lymphocytic leukemia (B-CLL) in five cases. The deleted region in the long arm of chromosome 7 in the 10 cases associated with B-LPDs was solely confined to the 7q22-q32 region. Conclusion: (1) The frequency of 7q interstitial deletions associated with B-LPDs is substantially high; (2) 7q interstitial deletions are not uncommon in B-CLL.
文摘AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of patients with hematological malignancies. All medical files of patients with malignant disease whose treatment was coordinated by the HematoOncology service of the Cayenne Hospital in French Guiana between the 1st of January 2010 and the 31 st of December 2012 were reviewed. Clinical data were extracted from the medical files and included: Demographic data, comorbidities, serological status for human immunodeficiency virus, human T-lymphotropic virus 1(HTLV1), hepatitis B virus and hepatitis C virusinfections, cytology and pathology diagnoses, disease extension, treatment, organization of disease management, and follow-up. The subgroup of patients with hematological malignancies and virus-related malignancies were reviewed. Cases involving patients with Kaposi sarcoma, and information on solid tumor occurrence in virus-infected patients in the whole patient population were included. Since the data were rendered anonymous, no informed consent was obtained from the patients for this retrospective analysis. Data were compiled using EXCEL® software, and the data presentation is descriptive only. The references search was guided by the nature of the data and discussion. RESULTS: In total, the clinical files of 594 patients(pts) were reviewed. Hematological malignancies were observed in 87 patients, and Kaposi sarcoma in 2 patients. In total, 70 patients had a viral infection, and 34 of these also had hematological malignancies. The hematological diagnoses were: Multiple myeloma in 27 pts, lymphoma(L) in 43 pts, myeloproliferative disorders in 17 pts and Kaposi sarcoma in two patients. The spectrum of non-Hodgkin lymphomas(NHL) was: Burkitt L(1 pt), follicular L(5 pts), chronic lymphocytic leukemia(5 pts), high-grade NHL(9 pts), mucosa-associated lymphoid tissue NHL(4 pts), T-cell lymphoma(4 pts), Adult T-cell lymphoma-leukemia(ATL)/lymphoma/leukemia(12 pts); three patients had Hodgkin disease. The spectrum of myeloproliferative diseases was: Chronic myelogenous leukemia(8 pts), thrombocytemia(5 pts) and acute leukemia(4 pts). There were no polycythemia vera, myelosclerosis, and myelodysplastic diseases. This appears to be due to bias in the recruitment process. The most important observations were: The specificity of HTLV1- related ATL malignancies, and the high incidence of virus infections in patients with hematological malignancies. Further, we noted several limitations regarding the treatment and organization of disease management. These were not related to the health care organization, but were due to a lack of board-certified hematooncology specialists, a lack of access to diagnostic tools(e.g., cytogenetic and molecular diagnosis, imaging techniques), the unavailability of radiotherapy, and the physical distance from mainland France. Yet the geography and cultures of the country also contributed to the encountered difficulties. These same limitations are seen in tropical countries with low and intermediate household incomes, but they are amplified by economic, social, and cultural issues. Thus, there is often little access to diagnostic procedures, adequate clinical management, and an unavailability of suitable medical treatments. Programs have been developed to establish centers of excellence, training in pathology diagnosis, and to provide free access to treatment.CONCLUSION: Management of hematological malignancies in tropical areas requires particular skills regarding specific features of these diseases and in terms of the affected populations, as well as solid public health policies.
