Objective:To investigate the effect of Fufang Danshen pill on bone marrow stem mobilization during myocardial scathe. Methods:Rat models with expansionary myocardial disease were established by Pituitrin and Furazol...Objective:To investigate the effect of Fufang Danshen pill on bone marrow stem mobilization during myocardial scathe. Methods:Rat models with expansionary myocardial disease were established by Pituitrin and Furazolidone. Experimental rats were divided into the contrast group, the myocardial scathe group (MS group), the myocardial scathe and Fufang Dansben pill group ( MS + FD group) and the myocardial scathe and fluvastatin group ( MS + FT group). The ratio of CD34^+ cells was examined at the 1^st, 3^nl and 6^th weekend. Index of heart structure and function including LVESD, LVEDD. LYEF, LVEDP and dp/dtmax were evaluated at the 6^th weekend. The HW/BW index was calculated. Results:In the MS group, the index of HW/BW, LVESD, LVEDD and LVEDP were obviously increased (P 〈 0.01 ) and index of dp/ dtmax and LVEF were obviously decreased (P 〈 0.05 ). The ratio of CD34^+ cells was significantly improved at the 1^at weekend and then reduced slowly with no difference from that of the contrast group at the 6th weekend. Compared the MS + FD group and the MS + FT group with the MS group, the index of HW/BW, LYESD, LYEDD and LYEDP of were signifi cantly decreased ( P 〈 0.05 ) and index of dp/dtmax and LVEF were increased (P 〈 0.01 ). The ratio of CD34^+ cells was significantly higher at the 1^st, 3^nl and 6^th weekend, but had no statistic meaning at 3^nl and 6^th weekend (P 〉 0.05 ). Conclusion:Pituitrin and Furazolidone can be used to establish rat models with expansionary myocardial disease. There has bone marrow stem mobilization during the early period of myocardial scathe. Fufang Danshen pill has effect on improving bone marrow stem mobilization, lightening the expansionary degree of heart and protecting the heart function. The effect of Fufang Danshen pill is as same as that of fluvastatin.展开更多
Objective: To investigate the expression of neuropilin-1 (NP-1) gene in bone marrow stromal cells (BMSCs) from myeloid leukemia (AML and CML) and normal individuals. Methods: Mononuclear cells were isolated from bone ...Objective: To investigate the expression of neuropilin-1 (NP-1) gene in bone marrow stromal cells (BMSCs) from myeloid leukemia (AML and CML) and normal individuals. Methods: Mononuclear cells were isolated from bone marrow (BM) of CML (14 cases), AML (12 cases) and normal individuals (20 cases). Adherent cells (i.e. BMSCs) were collected after long-term culture in vitro. The expression of NP-1 gene in three groups was detected respectively by reverse-transcription polymerase chain reaction (RT-PCR). Results: The long-term culture of BMSCs was successfully established. The expression level of NP-1 gene was significantly lower in BMSCs from AML (47.1%) and CML (50%) than in normal individuals (85%). Conclusion: NP-1 gene is expressed in BMSCs from some AML or CML patients and most normal individuals. The low-expression of NP-1 gene in BMSCs from AML or CML patients might be related with abnormality of regulation in hematopoiesis.展开更多
This study examined the signaling events induced by shikonin that lead to the induction of apoptosis in Bcr/ Abl-positive chronic myelogenous leukemia (CML) cells (e.g., K562, LAMA84). Treatment of K562 cells with...This study examined the signaling events induced by shikonin that lead to the induction of apoptosis in Bcr/ Abl-positive chronic myelogenous leukemia (CML) cells (e.g., K562, LAMA84). Treatment of K562 cells with shikonin (e.g., 0.5 pM) resulted in profound induction of apoptosis accompanied by rapid generation of reactive oxygen species (ROS), striking activation of c-Jun-N-terminal kinase (JNK) and p38, marked release of the mitochondrial proteins cytochrome c and Smac/DIABLO, activation of caspase-9 and -3, and cleavage of PARP. Scavenging of ROS completely blocked all of the above-mentioned events (i.e., JNK and p38 phosphorylation, cytochrome c and Smac/DIABLO release, caspase and PARP cleavage, as well as the induction of apoptosis) following shikonin treatment. Inhibition of JNK and knock-down of JNK1 significantly attenuated cytochrome c release, caspase cleavage and apoptosis, but did not affect shikonin-mediated ROS production. Additionally, inhibition of caspase activation completely blocked shikonin-induced apoptosis, but did not appreciably modify shikonin-mediated cytochrome c release or ROS generation. Altogether, these findings demonstrate that shikonin-induced oxidative injury operates at a proximal point in apoptotic signaling cascades, and subsequently activates the stress-related JNK pathway, triggers mitochondrial dysfunction, cytochrome c release, and caspase activation, and leads to apoptosis. Our data also suggest that shikonin may be a promising agent for the treatment of CML, as a generator of ROS.展开更多
We report a case of a 62-year old woman admitted to our hospital for multiple nodular metastatic liver lesions found by ultrasonography in a regular medical examination. Routine laboratory tests were normal. PET-CT sh...We report a case of a 62-year old woman admitted to our hospital for multiple nodular metastatic liver lesions found by ultrasonography in a regular medical examination. Routine laboratory tests were normal. PET-CT showed multiple bone lesions and nodular liver lesions. Liver biopsy revealed nodular infiltration of multiple myeloma with positive staining of kappa light chain. Further investigation of bone marrow aspiration, immunofixation and immunoelectrophoresis of serum protein, urine test for Bence-Jones protein, 132-microglobulin in serum and urine confirmed the diagnosis. The patient also coinfected with hepatitis C virus (HCV). With six cycles of chemotherapy with VAD schedule, she achieved complete remission. In this report, a literature review of liver lesions involving multiple myeloma is also provided.展开更多
Objective: To analyze Fms-like tyrosine kinase 3 (FLT3)/internal-tandem duplications (ITD) mutations in various kinds of hematologic malignancy patients. Methods: FLT3/ITD gene mutations were detected by polymer...Objective: To analyze Fms-like tyrosine kinase 3 (FLT3)/internal-tandem duplications (ITD) mutations in various kinds of hematologic malignancy patients. Methods: FLT3/ITD gene mutations were detected by polymerase chain reaction (PCR) in 103 acute myeloid leukemia (AML) cases, 63 acute lymphocytic leukemia (ALL) cases, 53 chronic myelogenous leukemia (CML) cases in chronic phase (CML-CP), 34 CML cases in blast crisis (CML-BC), 11 chronic lymphatic leukemia (CLL) cases, 36 myelodysplastic syndrome (MDS) cases, 9 multiple myeloma (MM) cases and 13 non-hodgkin's lymphoma (NHL) cases with marrow infiltration. Results: The expressions of FLT3/ITD gene mutations were detected in 22.3% AML cases, in 6.5% CML-BC cases, in 5.6% MDS cases and in 2.6% ALL cases. The two ALL cases with FLT3/ITD mutation were diagnosed as ALL-L2 with morphology and both with myeloid antigen expression, but finally were diagnosed as acute mixed-lineage leukemia after immunology examination. FLT3/ITD gene mutations were not detected in CML-CP, MM, NHL and CLL cases. In the 23 AML patients with FLT3/ITD gene mutation, including 2 of 8 M1 (2.5%), 8 of 33 M2 (24.2%), 7 of 24 M3 (29.3%), 2 of 11 M4 (18.2%), 3 of 21 M5 (14.3%), 1 of 5 M6 (20%), and 0 of 1 M7 cases, and there were no significant differences in the positive rates of FLT3/ITD mutations between the FAB subtypes (P 〉 0.05). Statistical analyses showed that in AML patients, FLT3/ITD was associated with a higher peripheral blood white cell (WBC) counts [(41.23 ± 32.56) x 109/L vs (11.36 ± 9.89) × 10^9/L (P 〈 0.01 )], higher percentage of bone marrow blast cells [(72.78 ± 21.79)% vs (51.26 ± 20.78)% (P 〈 0.05)], and higher cumulative relapse rates (63.6% vs 27.7%, P 〈 0.025) than those negative. Conclusion: FLT3/ITD gene mutation mainly occurred in AML patients, and might be a strong prognostic factor which was associated with high peripheral WBC counts, bone marrow blast cell proportion and a increased relapse risk in AML. Detection of FLT3/ITD gene mutation might provide insights to explore a more accurate genotyping of leukemia, differential diagnosis between AML and ALL, subdivide risk level in AML and estimate prognosis of leukemia.展开更多
Gastrointestinal stromal tumors (GISTs) are rare tumors, which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical ou...Gastrointestinal stromal tumors (GISTs) are rare tumors, which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, co- existance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection. Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered. During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma. To the best of our knowledge, this is the first report of the co-existence of multiple myeloma (MM) with GIST.展开更多
We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analy...We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analysis of the complementarity-determinining region III (CDR III) of the immunoglobulin heavy chain genes showed identical gene rearrangements in the CLL- and the MM-cell population. Our findings prove a common clonal tumor origin of both B-cell diseases in this patient.展开更多
Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity t...Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow (BM) niche is critical to the maintenance and retention of hematopoietic stem cells (HSC), including leukemia stem cells (LSC), and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.展开更多
OBJECTIVE Paget's disease is an uncommon breast malignancy and often misdiagnosed. If the patient is treated at an early stage, the prognos is is satisfactory. Our study analyzed the clinical characteristics of th...OBJECTIVE Paget's disease is an uncommon breast malignancy and often misdiagnosed. If the patient is treated at an early stage, the prognos is is satisfactory. Our study analyzed the clinical characteristics of the disease and the factors influencing the prognosis.METHOOS Fourty-five patients with Paget's disease who were admitted to our hospital were analyzed retrospectively.RESULTS The most common symptoms of the disease were erosion and a bleeding-like eczematoid change at the nipple/areola. Qf the 40 patients with an eczematoid change, 11 patients had verified Paget's disease with a palpable mass on physical examination, and 29 patients had verified Paget's disease with a nonpalpable mass. Only 5 patients manifested a mass with no eczematiod change. Thirteen patients had ipsilateral axillary lymphadenopathy. In this study, 25 cases were treated by radical mastectomy and 20 cases were treated by modified radical mastectomy.Five and 10-year survival rates for the patients with nonpalpable massesand for those with palpable masses were 95.5%, 78.6%, and 53.8%, 36.4% respectively. The former were significantly higher than the latter (P <0.01 and <0.05 respectively). Five and 10-year survival rates for the patients without underlying carcinoma (DClS/IDC) and for the patients with underlyingcarcinoma were 100%, 88.9% and 69.6%, 43.8% respectively. The former were significantly higher than the latter (P<0.05) Five and 10-year survival rates for the patients with negative lymph nodes and for the patients with positive lymph nodes were 92.0%, 76.5% and 50.0%, 25.0% respectively.The former were also significantly higher than the latter (P <0.05).CONCLUSION Treatment at an early stage is very important and influences the prognosis directly for Paget's disease of the breast. The survival rates of patients with nonpalpable masses without underlying carcinoma and without lymphadenopathy, were significantly higher than patients with palpable masses with underlying carcinoma and with lymphadenopathy respectively.There was significant statistical difference between each of the 2 groups.展开更多
Objective: To investigate the effects of soluble factors secreted by acute myeloid leukemia (AML) cells on the phenotypical and functional properties of DCs derived from normal mononuclear cells. Methods: Mononucl...Objective: To investigate the effects of soluble factors secreted by acute myeloid leukemia (AML) cells on the phenotypical and functional properties of DCs derived from normal mononuclear cells. Methods: Mononuclear cells were cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF), in the presence or absence of 24 h culture supematants from fresh pdmary AML cells, to generate immature DCs. The maturation of DCs was induced by cytokines IL-lbeta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and prostaglandin-2 (PGE-2). The phenotypic alterations of DCs and DCs-primed CD4+ T cells were evaluated using flow cytometry. Precursor frequency (PF) was calculated to monitor the allostimulatory effects of DCs on CD4^+ and CD8^+ T cells. Results:AML cell supernatant-treated DCs showed significantly lower expression of co-stimulatory molecules CDS0 and CD86, and reduced response to cytokines IL-1beta, IL-6, TNF-alpha, and PGE-2. The allostimulatory effects of AML cell supematant-treated DCs on CD4^+ and CD8^+ T cells were significantly lower than those of normal mature DCs [PF: (1.8 ±0.5)% vs. (5.2 ± 1.6)% for CD4^+ T cells, (2.1 ±0.6)% vs. (6.5 ± 2.0)% for CD8^+ T cells, P 〈 0.01]. These AML supernatantoinduced DCs could also induce allogeneic CD4^+ T cells to differentiate into CD4^+CD25high T cells, which had immunophenotyping characteristics of regulatory T cells, i.e. they expressed Foxp3 but not active maker CD69. Conclusion: This study demonstrates that soluble factors secreted by AML cells can inhibit development and functions of DCs. In addition, AML supernatant-induced DCs can induce the generation of CD4^+CD25^high T cells from CD4^+ T cells, which may be a mechanism of increased prevalence of CD4^+CD25^high regulatory T cells and immune dysfunction in AML patients.展开更多
IntroductionMultiple myeloma (MM) is a neoplastic plasma cell dyscrasia char-acterized by anemia; a monoclonal protein(M-protein) in the serum and/or urine; abnormal bone radiographs and bone pain;hypercal-cemia; ...IntroductionMultiple myeloma (MM) is a neoplastic plasma cell dyscrasia char-acterized by anemia; a monoclonal protein(M-protein) in the serum and/or urine; abnormal bone radiographs and bone pain;hypercal-cemia; and renal insuf.ciency or failure.According to the results of immunoelectrophoresis, patients are separated to Ig type (IgG, IgA, IgD, IgE and IgM); light chain; nonsecretory.展开更多
Extramedullary plasmacytoma (EMP) is rare in multiple myeloma, especially kidneys are involved. We report one case, including diagnosis and treatment. The purpose of this paper is to provide an attention on the extr...Extramedullary plasmacytoma (EMP) is rare in multiple myeloma, especially kidneys are involved. We report one case, including diagnosis and treatment. The purpose of this paper is to provide an attention on the extramedullary plasmacytoma disease, reducing the misdiagnose with this disease.展开更多
OBJECTIVE To study the mechanism of IFN on CML.METHODS Samples of 15 CML patients and 10 healthy controlswere studied. The flow cytometry was performed to identifycirculating pDCs. The concentration of IFN-α in serum...OBJECTIVE To study the mechanism of IFN on CML.METHODS Samples of 15 CML patients and 10 healthy controlswere studied. The flow cytometry was performed to identifycirculating pDCs. The concentration of IFN-α in serum and that inthe supernatant of peripheral blood mononuclear cells (PBMCs)cultured after stimulation with CpG ODN2216 were examinedboth in CML patients and in the healthy controlsRESULTS There was significant reduction in the numberof circulating pDCs, serum concentration of IFN-α and thecapacity of IFN-α producing PBMCs in CML patients comparedwith those in healthy control individuals (P < 0.001). After theactive treatment with IFN-α and hydroxyurea, the quantity andfunction of pDCs were increased in stabilized patients, especiallythe function of pDCs in 2 patients achieving major cytogeneticresponse (MCR). The proportion and function of pDCs and theserum levels of IFN were inversely correlated with both WBC andage of the patients with CML, and positively correlated with thestate of the illness.CONCLUSION CML patients had a reduced number anddysfunction of circulating pDCs. The active treatment with IFN inCML patients may be related to the restoration of pDCs.展开更多
OBJECTIVE: To study telomerase activity (TA) and its variation in bone marrow mononuclear cells from patients with myelodysplastic syndrome (MDS) at different stages in comparison with normal bone marrow cells and leu...OBJECTIVE: To study telomerase activity (TA) and its variation in bone marrow mononuclear cells from patients with myelodysplastic syndrome (MDS) at different stages in comparison with normal bone marrow cells and leukemic cells. METHODS: The TA was semi-quantitatively determined in mononuclear cells from 20 normal bone marrow samples, 21 patients with MDS at different stages and 32 cases of acute leukemia by using a polymerase chain reaction-enzyme linked immuno-sorben assay (PCR-ELISA) kit. RESULTS: The TA in normal bone marrow cells was in the range of 0 to 0.3 units (U) with a mean of 0.11 +/- 0.08 U. Among them, 3 samples were considered positive in accordance with the standard recommended by the kit's pamphlet. In bone marrow cells from patients with acute leukemia, the TA was ranging from 0 to 0.96 U with a mean value of 0.42 +/- 0.26 U. The positive rate was 78.1% which was significantly different from that in normal bone marrow (BM) (P展开更多
文摘Objective:To investigate the effect of Fufang Danshen pill on bone marrow stem mobilization during myocardial scathe. Methods:Rat models with expansionary myocardial disease were established by Pituitrin and Furazolidone. Experimental rats were divided into the contrast group, the myocardial scathe group (MS group), the myocardial scathe and Fufang Dansben pill group ( MS + FD group) and the myocardial scathe and fluvastatin group ( MS + FT group). The ratio of CD34^+ cells was examined at the 1^st, 3^nl and 6^th weekend. Index of heart structure and function including LVESD, LVEDD. LYEF, LVEDP and dp/dtmax were evaluated at the 6^th weekend. The HW/BW index was calculated. Results:In the MS group, the index of HW/BW, LVESD, LVEDD and LVEDP were obviously increased (P 〈 0.01 ) and index of dp/ dtmax and LVEF were obviously decreased (P 〈 0.05 ). The ratio of CD34^+ cells was significantly improved at the 1^at weekend and then reduced slowly with no difference from that of the contrast group at the 6th weekend. Compared the MS + FD group and the MS + FT group with the MS group, the index of HW/BW, LYESD, LYEDD and LYEDP of were signifi cantly decreased ( P 〈 0.05 ) and index of dp/dtmax and LVEF were increased (P 〈 0.01 ). The ratio of CD34^+ cells was significantly higher at the 1^st, 3^nl and 6^th weekend, but had no statistic meaning at 3^nl and 6^th weekend (P 〉 0.05 ). Conclusion:Pituitrin and Furazolidone can be used to establish rat models with expansionary myocardial disease. There has bone marrow stem mobilization during the early period of myocardial scathe. Fufang Danshen pill has effect on improving bone marrow stem mobilization, lightening the expansionary degree of heart and protecting the heart function. The effect of Fufang Danshen pill is as same as that of fluvastatin.
基金This work was supported by a grant from National Scaling Height Programm (95-zhuan-10).
文摘Objective: To investigate the expression of neuropilin-1 (NP-1) gene in bone marrow stromal cells (BMSCs) from myeloid leukemia (AML and CML) and normal individuals. Methods: Mononuclear cells were isolated from bone marrow (BM) of CML (14 cases), AML (12 cases) and normal individuals (20 cases). Adherent cells (i.e. BMSCs) were collected after long-term culture in vitro. The expression of NP-1 gene in three groups was detected respectively by reverse-transcription polymerase chain reaction (RT-PCR). Results: The long-term culture of BMSCs was successfully established. The expression level of NP-1 gene was significantly lower in BMSCs from AML (47.1%) and CML (50%) than in normal individuals (85%). Conclusion: NP-1 gene is expressed in BMSCs from some AML or CML patients and most normal individuals. The low-expression of NP-1 gene in BMSCs from AML or CML patients might be related with abnormality of regulation in hematopoiesis.
基金Acknowledgments This work was supported by grants from the National High Technology Research and Development Program of China (863 Program) (2006AA02A306), the National Natural Science Foundation of China (No. 39900082) and the PhD Program Foundation of Ministry of Education of China (No. 204090188). We thank Dr Courtney M Heney (Massachusetts General Hospital, Harvard University) for critically reading the manuscript.
文摘This study examined the signaling events induced by shikonin that lead to the induction of apoptosis in Bcr/ Abl-positive chronic myelogenous leukemia (CML) cells (e.g., K562, LAMA84). Treatment of K562 cells with shikonin (e.g., 0.5 pM) resulted in profound induction of apoptosis accompanied by rapid generation of reactive oxygen species (ROS), striking activation of c-Jun-N-terminal kinase (JNK) and p38, marked release of the mitochondrial proteins cytochrome c and Smac/DIABLO, activation of caspase-9 and -3, and cleavage of PARP. Scavenging of ROS completely blocked all of the above-mentioned events (i.e., JNK and p38 phosphorylation, cytochrome c and Smac/DIABLO release, caspase and PARP cleavage, as well as the induction of apoptosis) following shikonin treatment. Inhibition of JNK and knock-down of JNK1 significantly attenuated cytochrome c release, caspase cleavage and apoptosis, but did not affect shikonin-mediated ROS production. Additionally, inhibition of caspase activation completely blocked shikonin-induced apoptosis, but did not appreciably modify shikonin-mediated cytochrome c release or ROS generation. Altogether, these findings demonstrate that shikonin-induced oxidative injury operates at a proximal point in apoptotic signaling cascades, and subsequently activates the stress-related JNK pathway, triggers mitochondrial dysfunction, cytochrome c release, and caspase activation, and leads to apoptosis. Our data also suggest that shikonin may be a promising agent for the treatment of CML, as a generator of ROS.
文摘We report a case of a 62-year old woman admitted to our hospital for multiple nodular metastatic liver lesions found by ultrasonography in a regular medical examination. Routine laboratory tests were normal. PET-CT showed multiple bone lesions and nodular liver lesions. Liver biopsy revealed nodular infiltration of multiple myeloma with positive staining of kappa light chain. Further investigation of bone marrow aspiration, immunofixation and immunoelectrophoresis of serum protein, urine test for Bence-Jones protein, 132-microglobulin in serum and urine confirmed the diagnosis. The patient also coinfected with hepatitis C virus (HCV). With six cycles of chemotherapy with VAD schedule, she achieved complete remission. In this report, a literature review of liver lesions involving multiple myeloma is also provided.
文摘Objective: To analyze Fms-like tyrosine kinase 3 (FLT3)/internal-tandem duplications (ITD) mutations in various kinds of hematologic malignancy patients. Methods: FLT3/ITD gene mutations were detected by polymerase chain reaction (PCR) in 103 acute myeloid leukemia (AML) cases, 63 acute lymphocytic leukemia (ALL) cases, 53 chronic myelogenous leukemia (CML) cases in chronic phase (CML-CP), 34 CML cases in blast crisis (CML-BC), 11 chronic lymphatic leukemia (CLL) cases, 36 myelodysplastic syndrome (MDS) cases, 9 multiple myeloma (MM) cases and 13 non-hodgkin's lymphoma (NHL) cases with marrow infiltration. Results: The expressions of FLT3/ITD gene mutations were detected in 22.3% AML cases, in 6.5% CML-BC cases, in 5.6% MDS cases and in 2.6% ALL cases. The two ALL cases with FLT3/ITD mutation were diagnosed as ALL-L2 with morphology and both with myeloid antigen expression, but finally were diagnosed as acute mixed-lineage leukemia after immunology examination. FLT3/ITD gene mutations were not detected in CML-CP, MM, NHL and CLL cases. In the 23 AML patients with FLT3/ITD gene mutation, including 2 of 8 M1 (2.5%), 8 of 33 M2 (24.2%), 7 of 24 M3 (29.3%), 2 of 11 M4 (18.2%), 3 of 21 M5 (14.3%), 1 of 5 M6 (20%), and 0 of 1 M7 cases, and there were no significant differences in the positive rates of FLT3/ITD mutations between the FAB subtypes (P 〉 0.05). Statistical analyses showed that in AML patients, FLT3/ITD was associated with a higher peripheral blood white cell (WBC) counts [(41.23 ± 32.56) x 109/L vs (11.36 ± 9.89) × 10^9/L (P 〈 0.01 )], higher percentage of bone marrow blast cells [(72.78 ± 21.79)% vs (51.26 ± 20.78)% (P 〈 0.05)], and higher cumulative relapse rates (63.6% vs 27.7%, P 〈 0.025) than those negative. Conclusion: FLT3/ITD gene mutation mainly occurred in AML patients, and might be a strong prognostic factor which was associated with high peripheral WBC counts, bone marrow blast cell proportion and a increased relapse risk in AML. Detection of FLT3/ITD gene mutation might provide insights to explore a more accurate genotyping of leukemia, differential diagnosis between AML and ALL, subdivide risk level in AML and estimate prognosis of leukemia.
文摘Gastrointestinal stromal tumors (GISTs) are rare tumors, which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, co- existance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection. Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered. During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma. To the best of our knowledge, this is the first report of the co-existence of multiple myeloma (MM) with GIST.
文摘We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analysis of the complementarity-determinining region III (CDR III) of the immunoglobulin heavy chain genes showed identical gene rearrangements in the CLL- and the MM-cell population. Our findings prove a common clonal tumor origin of both B-cell diseases in this patient.
基金funding from Guangzhou Pearl River of Science & Technology New Star (Grant No. 2011J2200069)supported in part by grants from the National Institutes of Health (Grant No. P01 CA055164)+2 种基金MD Anderson Cancer Center Support (Grant No. CA016672)the Paul and Mary Haas Chair in Genetics to Michael Andreeffby the University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center to Bing Z. Carter
文摘Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow (BM) niche is critical to the maintenance and retention of hematopoietic stem cells (HSC), including leukemia stem cells (LSC), and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.
文摘OBJECTIVE Paget's disease is an uncommon breast malignancy and often misdiagnosed. If the patient is treated at an early stage, the prognos is is satisfactory. Our study analyzed the clinical characteristics of the disease and the factors influencing the prognosis.METHOOS Fourty-five patients with Paget's disease who were admitted to our hospital were analyzed retrospectively.RESULTS The most common symptoms of the disease were erosion and a bleeding-like eczematoid change at the nipple/areola. Qf the 40 patients with an eczematoid change, 11 patients had verified Paget's disease with a palpable mass on physical examination, and 29 patients had verified Paget's disease with a nonpalpable mass. Only 5 patients manifested a mass with no eczematiod change. Thirteen patients had ipsilateral axillary lymphadenopathy. In this study, 25 cases were treated by radical mastectomy and 20 cases were treated by modified radical mastectomy.Five and 10-year survival rates for the patients with nonpalpable massesand for those with palpable masses were 95.5%, 78.6%, and 53.8%, 36.4% respectively. The former were significantly higher than the latter (P <0.01 and <0.05 respectively). Five and 10-year survival rates for the patients without underlying carcinoma (DClS/IDC) and for the patients with underlyingcarcinoma were 100%, 88.9% and 69.6%, 43.8% respectively. The former were significantly higher than the latter (P<0.05) Five and 10-year survival rates for the patients with negative lymph nodes and for the patients with positive lymph nodes were 92.0%, 76.5% and 50.0%, 25.0% respectively.The former were also significantly higher than the latter (P <0.05).CONCLUSION Treatment at an early stage is very important and influences the prognosis directly for Paget's disease of the breast. The survival rates of patients with nonpalpable masses without underlying carcinoma and without lymphadenopathy, were significantly higher than patients with palpable masses with underlying carcinoma and with lymphadenopathy respectively.There was significant statistical difference between each of the 2 groups.
基金grants from the National Outstanding Young Investigator Program (30225038)Anhui Provincial Natural Science Foundation (070413094)+1 种基金Scientific Research Fund of Anhui Provincial Education Department (2006KJ072C)Science and Technological Fund of Anhui Province for Outstanding Youth.
文摘Objective: To investigate the effects of soluble factors secreted by acute myeloid leukemia (AML) cells on the phenotypical and functional properties of DCs derived from normal mononuclear cells. Methods: Mononuclear cells were cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF), in the presence or absence of 24 h culture supematants from fresh pdmary AML cells, to generate immature DCs. The maturation of DCs was induced by cytokines IL-lbeta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and prostaglandin-2 (PGE-2). The phenotypic alterations of DCs and DCs-primed CD4+ T cells were evaluated using flow cytometry. Precursor frequency (PF) was calculated to monitor the allostimulatory effects of DCs on CD4^+ and CD8^+ T cells. Results:AML cell supernatant-treated DCs showed significantly lower expression of co-stimulatory molecules CDS0 and CD86, and reduced response to cytokines IL-1beta, IL-6, TNF-alpha, and PGE-2. The allostimulatory effects of AML cell supematant-treated DCs on CD4^+ and CD8^+ T cells were significantly lower than those of normal mature DCs [PF: (1.8 ±0.5)% vs. (5.2 ± 1.6)% for CD4^+ T cells, (2.1 ±0.6)% vs. (6.5 ± 2.0)% for CD8^+ T cells, P 〈 0.01]. These AML supernatantoinduced DCs could also induce allogeneic CD4^+ T cells to differentiate into CD4^+CD25high T cells, which had immunophenotyping characteristics of regulatory T cells, i.e. they expressed Foxp3 but not active maker CD69. Conclusion: This study demonstrates that soluble factors secreted by AML cells can inhibit development and functions of DCs. In addition, AML supernatant-induced DCs can induce the generation of CD4^+CD25^high T cells from CD4^+ T cells, which may be a mechanism of increased prevalence of CD4^+CD25^high regulatory T cells and immune dysfunction in AML patients.
文摘IntroductionMultiple myeloma (MM) is a neoplastic plasma cell dyscrasia char-acterized by anemia; a monoclonal protein(M-protein) in the serum and/or urine; abnormal bone radiographs and bone pain;hypercal-cemia; and renal insuf.ciency or failure.According to the results of immunoelectrophoresis, patients are separated to Ig type (IgG, IgA, IgD, IgE and IgM); light chain; nonsecretory.
文摘Extramedullary plasmacytoma (EMP) is rare in multiple myeloma, especially kidneys are involved. We report one case, including diagnosis and treatment. The purpose of this paper is to provide an attention on the extramedullary plasmacytoma disease, reducing the misdiagnose with this disease.
基金supported by a grant from the Science and Technology Planning Project of Gansu Province,China(No.2005LZ0627).
文摘OBJECTIVE To study the mechanism of IFN on CML.METHODS Samples of 15 CML patients and 10 healthy controlswere studied. The flow cytometry was performed to identifycirculating pDCs. The concentration of IFN-α in serum and that inthe supernatant of peripheral blood mononuclear cells (PBMCs)cultured after stimulation with CpG ODN2216 were examinedboth in CML patients and in the healthy controlsRESULTS There was significant reduction in the numberof circulating pDCs, serum concentration of IFN-α and thecapacity of IFN-α producing PBMCs in CML patients comparedwith those in healthy control individuals (P < 0.001). After theactive treatment with IFN-α and hydroxyurea, the quantity andfunction of pDCs were increased in stabilized patients, especiallythe function of pDCs in 2 patients achieving major cytogeneticresponse (MCR). The proportion and function of pDCs and theserum levels of IFN were inversely correlated with both WBC andage of the patients with CML, and positively correlated with thestate of the illness.CONCLUSION CML patients had a reduced number anddysfunction of circulating pDCs. The active treatment with IFN inCML patients may be related to the restoration of pDCs.
文摘OBJECTIVE: To study telomerase activity (TA) and its variation in bone marrow mononuclear cells from patients with myelodysplastic syndrome (MDS) at different stages in comparison with normal bone marrow cells and leukemic cells. METHODS: The TA was semi-quantitatively determined in mononuclear cells from 20 normal bone marrow samples, 21 patients with MDS at different stages and 32 cases of acute leukemia by using a polymerase chain reaction-enzyme linked immuno-sorben assay (PCR-ELISA) kit. RESULTS: The TA in normal bone marrow cells was in the range of 0 to 0.3 units (U) with a mean of 0.11 +/- 0.08 U. Among them, 3 samples were considered positive in accordance with the standard recommended by the kit's pamphlet. In bone marrow cells from patients with acute leukemia, the TA was ranging from 0 to 0.96 U with a mean value of 0.42 +/- 0.26 U. The positive rate was 78.1% which was significantly different from that in normal bone marrow (BM) (P