TNF与急性早幼粒细胞白血病

１６例急性早幼粒细胞白自病患者血清ＴＮＦ活性明显高于正常对照（Ｐ＜０．０５），而经ＲＡ诱导分化治疗中期及治疗后明显降低（Ｐ＜０．０５），但仍高于正常对照组。各治疗时相的外周白细胞浆内ＴＮＦ平均水平及正常对照间均无明显差别（Ｐ＞０．０５），治疗前及治疗中期胞浆ＴＮＦ活性升高率明显高于治疗后或正常对照（Ｐ＜０．０５）。相关分析表明：血清ＴＮＦ活性水平与外周血ＷＢＣ总数或骨髓ＧＭ－ＣＦＵ无明显相关，而与     

APL患者ATRA诱导分化后G—CSF分泌水平升高的分子机制研究

目的探讨ATRA诱导后患者血清G—CSF升高的机制是否与原代APL细胞分泌G—CSF变化有关，并探讨其变化的分子机制。方法显微镜下直接计数原代APL细胞的增殖性变化。采用酶联免疫ELISA法测定原代APL细胞培养上清G—CSF水平的变化，RT-PCR方法测定Nm23或G-CSF mRNA表达水平。结果ATRA诱导治疗后，APL患者外周血白细胞明显升高，平均12天达到高峰，并且以中晚幼粒细胞为主。APL患者血清G—CSF水平升高，原代APL细胞体外培养24小时后，上清中的G—CSF分泌水平显著升高（P〈0．05）。RT—PCR实验结果表明原代APL细胞G—CSF mRNA表达升高，与Nm23表达变化成相反趋势。结论ATRA诱导高表达的G—CSF可能与Nm23降低有关。     

Acute promyelocytic leukaemia with t(11;17)(q23;q12-21) and a good initial response to prolonged ATRA and combination chemotherapy

Acute myeloid leukaemia (AML) of FAB subtype M3 is associated with t(15;17)(q22;q21) and a relatively good prognosis when treated with all- trans retinoic acid (ATRA) and combination chemotherapy. Rarely, alternative balanced translocations have been described in this subtype of AML. The translocation t(11;17)(q23;q21) leading to a PLZF/RARα rearrangement has been described in a very small number of cases and has been associated with a poor response to ATRA and an adverse prognosis. We describe a case of AML FAB type M3 with this translocation who entered morphological and cytogenetic complete remission after concurrent prolonged ATRA and one course of induction chemotherapy and remains in morphological and molecular remission at 10 months after presentation. This diagnosis therefore may not always be associated with a poor initial response to treatment.     

Autologous Is Superior to Allogeneic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukemia in Second Complete Remission

To identify favored choice of transplantation in patients with acute promyelocytic leukemia (APL) in second complete remission, we studied 294 patients with APL in second complete remission (CR2) receiving allogeneic (n = 232) or autologous (n = 62) hematopoietic cell transplantation (HCT) reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR) from 1995 to 2006, including 155 with pre-HCT PML/RAR∝ status (49% of allogeneic and 66% of autologous). Patient characteristics and transplantation characteristics, including treatment-related mortality, overall survival (OS), and disease-free survival, were collected and analyzed for both univariate and multivariate outcomes. With median follow-up of 115 (allogeneic) and 72 months (autologous), 5-year disease-free survival (DFS) favored autologous with 63% (49% to 75%), compared with allogeneic at 50% (44% to 57%) (P = .10). OS was 75% (63% to 85%) versus 54% (48% to 61%) (P = .002), for autologous and allogeneic transplantation, respectively. Multivariate analysis showed significantly worse DFS after allogeneic HCT (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.16 to 3.06; P = .011) and age > 40 years (HR, 2.30; 95% CI, 1.44 to 3.67; P = .0005). OS was significantly worse after allogeneic HCT (HR, 2.66; 95% CI, 1.52 to 4.65; P = .0006); age > 40 (HR, 3.29; 95% CI, 1.95 to 5.54; P < .001), and first complete remission < 12 months (HR, 1.56; 95% CI, 1.07 to 2.26; P = .021). Positive pre-HCT PML-RAR∝ status in 17 of 114 allogeneic and 6 of 41 receiving autologous transplantation did not influence relapse, treatment failure, or survival in either group. The survival advantage for autografting was attributable to increased treatment-related mortality (TRM) in the allogeneic group of 30% compared to 2% in the autologous group, in addition to the added mortality associated with GVHD. We conclude that autologous HCT yields superior OS for APL in CR2. Long-term DFS in autologous recipients, even with minimal residual disease–positive grafts, remains an important subject for further study.     

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??Abstract??Objective To explore the role of miR-125b in pediatric classical APL?? in order to seek new therapeutic strategies for drug resistant APL. Methods The target genes of miR-125b were predicted online?? validated by Dual-luciferase assay and western blot assay. MiR-125b expression levels were measured in 33 matched-pair APL samples??treated in the First Affiliated Hospital of Sun Yat-sen University and other members of South China Children APL Cooperative Group from March 2007 to September2012??at initial diagnosis and complete remission ??CR?? and in 5 relapsed patients by qRT-PCR. Proliferation and apoptosis were analyzed respectively using the RNA transfection?? MTT assay and flow cytometry. Results The expression of miR-125b was up-regulated in pediatric APL at diagnosis and relapse bone marrow samples?? but returned to normal after complete remission?? miR-125b could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor Bak1. Remarkably??it was also found to be up-regulated in leukemic drug-resistant cells??NB4-R1??NB4-R2??HL-60/DOX???? and overexpression of exogenous miR-125b could increase their resistance to therapeutic drugs. Conclusion MiR-125b can regulate pediatric classical APL cells proliferation?? apoptosis and drug resistance by repressing BAK1 protein expression.     

Outcome of pregnancy in women treated with all-trans retinoic acid; A case report and review of literature

Abstract

All-trans-retinoic acid (ATRA) has been proved to be an effective treatment for acute promyelocytic leukemia (APL), inducing remission in more than 90% of cases. Treatment of APL in pregnancy is controversial as the use of ATRA has been questioned due to the teratogenic effect of retinoids. We report a case of pregnancy in a woman exposed to ATRA during the first trimester. The baby was born healthy, without any anomalies. Review of all reported cases of the use of ATRA in pregnancy revealed no serious adverse outcomes or congenital anomalies although only very few cases had exposure in the first trimester.     

Treatment of Newly Diagnosed Acute Promyelocytic Leukemia (APL) by All Transretinoic Acid (ATRA) Combined with Chemotherapy: The European Experience

All transretinoic acid (ATRA) gives complete remission (CR) rates of 80 to 90% in newly diagnosed acute promyelocytic leukemia (APL). However, it has two major drawbracks (1) a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome (2) rapid relapse with maintenance therapy using ATRA alone or low dose chemotherapy. The French APL group therefore designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. These results were confirmed by the Chinese, Japanese and New York groups. Our group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy) and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low dose chemotherapy or both.     

亚砷酸治疗急性早幼粒细胞白血病的临床研究

目的:对亚砷酸和全反式维甲酸(ATRA)在急性早幼粒细胞白血病(APL)治疗中进行临床的比较.方法:对153例APL病人进行回顾性统计分析.结果:ATRA组出现一过性白细胞增高(95.25%),维甲酸综合征(54.64%)及较为多见的DIC(84.72%vs17.54%),而亚砷酸组此类现象的发生率很低,同时亚砷酸组令人关注的肝肾毒性收与ATRA组比较并无统计学差异.结论:在初诊APL治疗中,选用亚砷酸治疗更为安全、可靠,有利于病人恢复健康.     

急性早幼粒细胞白血病患者白细胞介素6测定与意义分析

本文用IL-6依赖细胞株MH60-BSF2检测12例患者血清与白血病细胞内IL-6活性。结果发现正常对照血清IL-6平均<10U/ml,白细胞内IL-6活性多数测不到(仅1例为5U/2×10~5)。APL患者治疗前期、中期(白细胞增殖期)及后期(缓解期)血清IL-6活性分别为36.06±15.72U/ml、41.5±/5.0U/ml和22.12±12.02U/ml:治疗中期似有升高(P>0.05),治疗后期下降(P<0.05);外周白细胞内IL-6活性分别为8.98±8.6U/2×10~5细胞、5.36±4.16U/2×10~5细胞和5.95±3.68U/2×19~5细胞,治疗前似较高(P>0.05),治疗后无明显变化。APL瘤细胞在体外比正常白细胞有更高的IL-6活性(P<0.05)。相关分析表明APL患者外周总白细胞数,骨髓L-CFU及GM-CFU均与IL-6活性变化不相关(P<0.05)。