急性髓细胞性白血病(acu te myel o id leukemia,AML)的骨髓或外周血原始细胞一般需≥20%,但是伴t(8;21)(q22;q22.1);RUNX1-RUNX1T1(AML1-ETO)、inv(16)(p13.1q22)或t(16;16)(p13.1;q22);CBFB-MYH11和PML-RARA的AML,原始细胞比例可以低...急性髓细胞性白血病(acu te myel o id leukemia,AML)的骨髓或外周血原始细胞一般需≥20%,但是伴t(8;21)(q22;q22.1);RUNX1-RUNX1T1(AML1-ETO)、inv(16)(p13.1q22)或t(16;16)(p13.1;q22);CBFB-MYH11和PML-RARA的AML,原始细胞比例可以低于20%,但临床上少见。本研究报道1例原始细胞<20%伴RUNX1-RUNX1T1(AML1-ETO)阳性的AML病例。展开更多
Granulocytic sarcoma is a form of acute myeloid leukemia which may occur in any anatomical site. Isolated pancreatic granulocytic sarcoma is however, extremely rare. Translocation t(8;21) is the most common cytogeneti...Granulocytic sarcoma is a form of acute myeloid leukemia which may occur in any anatomical site. Isolated pancreatic granulocytic sarcoma is however, extremely rare. Translocation t(8;21) is the most common cytogenetic abnormality found in leukemia patients with granulocytic sarcoma and is associated with a relatively good prognosis when treated with chemotherapy. Variants of the t(8;21) are uncommon and account for approximately 3% to 4% of acute myeloid leukemia associated with t(8;21) and are rarely described in acute myeloid leukemia cases associated with granulocytic sarcoma. We report here a patient with acute myeloid leukemia and a novel variant t(8;9;21)(q22;p24;q22) with suspected granulocytic sarcoma in pancreas. A dual-color fluorescence in situ hybridization analysis with RUNX1T1 and RUNX1 probes, revealed the presence of an RUNX1/RUNX1T1 fusion signal in this translocation. To the best of our knowledge, a variant of t(8;21) in GS was rarely described and the involvement of the 9q22 region is the first time described here even in isolated AML-M2. We conclude that further accumulation of similar cases is needed and that genetic exploring of variants of t(8;21) may be helpful for a better understanding of molecular pathogenetic mechanism.展开更多
Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subseque...Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall survival(HR = 3.50,2.32,and 4.34;95%CI 1.56-7.82,1.09-4.97,and 1.98-9.53;P = 0.002,0.030,and <0.001,respectively) in all patients.Conclusions:Testing for WTl transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission.A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients.展开更多
文摘目的探讨RUNX1-RUNX1T1+急性髓细胞白血病(AML)RUNX1-RUNX1T1转录本(融合转录本)的动态变化及其对预后的指导作用。方法回顾性队列研究,纳入2006年10月1日至2015年3月31日在首都医科大学附属北京儿童医院(我院)采用BCH-AML 05方案治疗的全部RUNX1-RUNX1T1+AML患儿,根据初诊(time point 0,TP0)、诱导Ⅰ后(TP1)、诱导Ⅱ后(TP2)、巩固Ⅰ后(TP3)、巩固Ⅱ后(TP4)和巩固Ⅲ后(TP5)融合转录本的检测情况,相应地分为高表达组和低表达组,分组界值分别为每104GUS中融合转录本拷贝数10~4、10~3、10~2、10、1和0,随访至2017年12月31日。采用χ2检验比较初诊高表达组和低表达组临床和生物学特征的差异;Kaplan-Meier法分析患儿5年总生存(OS)和无复发生存(RFS),通过Log-rank检验比较组间差异,以Cox比例风险回归模型分析影响患儿5年OS和RFS的独立预后因素。结果符合本文纳入标准的患儿52例,男27例,中位年龄8(2~14)岁;2例TP1时失访,21例在随访中死亡,其余29例中位随访时间62.2(34.0~134.3)个月。(1)初诊高表达组(17/50)和低表达组(33/50)患儿的年龄、性别、WBC、Hb、PLT计数和骨髓幼稚细胞数、除CD15(P=0.004)外的免疫学表型、TP1~TP5的MRD差异均无统计学意义。(2)单因素分析表明,TP1和TP5融合转录本水平与患儿的5年OS和RFS相关,性别、初诊PLT与5年OS相关,初诊WBC与5年RFS相关。多因素分析显示,TP1时融合转录本水平>103拷贝/104GUS是5年OS的独立不良因素(HR=0.095,95%:CI:0.011~0.860,P=0.036)。结论 RUNX1-RUNX1T1+AML患儿第1次诱导治疗结束后融合转录本水平是患儿长期预后的独立影响因素。
文摘急性髓细胞性白血病(acu te myel o id leukemia,AML)的骨髓或外周血原始细胞一般需≥20%,但是伴t(8;21)(q22;q22.1);RUNX1-RUNX1T1(AML1-ETO)、inv(16)(p13.1q22)或t(16;16)(p13.1;q22);CBFB-MYH11和PML-RARA的AML,原始细胞比例可以低于20%,但临床上少见。本研究报道1例原始细胞<20%伴RUNX1-RUNX1T1(AML1-ETO)阳性的AML病例。
文摘Granulocytic sarcoma is a form of acute myeloid leukemia which may occur in any anatomical site. Isolated pancreatic granulocytic sarcoma is however, extremely rare. Translocation t(8;21) is the most common cytogenetic abnormality found in leukemia patients with granulocytic sarcoma and is associated with a relatively good prognosis when treated with chemotherapy. Variants of the t(8;21) are uncommon and account for approximately 3% to 4% of acute myeloid leukemia associated with t(8;21) and are rarely described in acute myeloid leukemia cases associated with granulocytic sarcoma. We report here a patient with acute myeloid leukemia and a novel variant t(8;9;21)(q22;p24;q22) with suspected granulocytic sarcoma in pancreas. A dual-color fluorescence in situ hybridization analysis with RUNX1T1 and RUNX1 probes, revealed the presence of an RUNX1/RUNX1T1 fusion signal in this translocation. To the best of our knowledge, a variant of t(8;21) in GS was rarely described and the involvement of the 9q22 region is the first time described here even in isolated AML-M2. We conclude that further accumulation of similar cases is needed and that genetic exploring of variants of t(8;21) may be helpful for a better understanding of molecular pathogenetic mechanism.
基金supported by Grants from the Key Program of the National Natural Science Foundation of China(81230013)the Major State Basic Research Development Program of China(973 Program,2013CB733701)+2 种基金the Nature Science Foundation of China(81170483,81570130 and 81370639)the Beijing Municipal Science and Technology Commission(Z141100000214011)support from the NIHR Biomedical Research Centre funding scheme
文摘Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall survival(HR = 3.50,2.32,and 4.34;95%CI 1.56-7.82,1.09-4.97,and 1.98-9.53;P = 0.002,0.030,and <0.001,respectively) in all patients.Conclusions:Testing for WTl transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission.A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients.
