Acute promyelocytic leukemia (APL) represents the first example o f a human cancer successfully treated with a differentiation reducer, all-trans retinoic acid. APL is also characterized by a specific chromosome trans...Acute promyelocytic leukemia (APL) represents the first example o f a human cancer successfully treated with a differentiation reducer, all-trans retinoic acid. APL is also characterized by a specific chromosome translocution t (15; 17). In this work, using techniques of molecular biology, we demonstrated that the gene coding for the retinoic acid receptor alpha (RARA), normally located on chromosome 17, was disrupted by the t (15; 17) and fused with the PML gene on chromosome 15. The chromosome 17 breaks were mapped consistently within the second intron of the RARA gene while the chromosome 15 breaks were clustered in two limited regions within the PML gene. Molecular cloning and sequence analysis of part of the PML gene allowed to establish a specific "nested" reverse transcription/polymerase chain reaction (PCR) procedure to characterize the expression patterns of the PML-RARA fusion gene. Different iso forms of the fusion transcripts were discovered which were produced as a result of distinct PML gene rearrangements. The biological activity of the PML-RARA fusion gene and its iso forms should be further explored.展开更多
Objective： To investigate the distribution and clonality of TCR Va subfamily T cells in patients with acute promyelocytic leukemia （APL）. Methods： The complementary determining region 3 （CDR3） of TCR Va 29 subfa...Objective： To investigate the distribution and clonality of TCR Va subfamily T cells in patients with acute promyelocytic leukemia （APL）. Methods： The complementary determining region 3 （CDR3） of TCR Va 29 subfamily genes in peripheral blood mononuclear cells from 9 APL patients were amplified using RT-PCR. The positive products were further analyzed to identity the clonality of T cells by GeneScan technique. Results： One to seven of TCR Va subfamilies could be detected in peripheral blood T cells from 9 cases with APL, the frequent expression of Va subfamilies predominated in Vα3 and Va19. Clonal expanded T cells could be detected in 8 APL patients, which predominant used Va3, Va26 or Va27 （3 out of 8 cases）. However, almost all Va subfamilies with polyclonal expansion could be detected in peripheral blood T cells from 10 cases of normal individuals. Conclusion： Remarkable skew distribution and clonal expansion of TCR Va subfamilies T cells is the common feature in patients with APL. Clonal expansion of T cells might reflect a response in host to APL cell associated antigen, whether these expanded T cells have the ability for specific cytotoxicity against APL cells, remains an open question.展开更多
Chromosomal translocation t(15; 17) is a specific marker of acute promyelocytic leukemia (APL). In this study, molecular cloning of the t(15;17) breakpoint was carried out in a Chinese APL patient. It has been shown t...Chromosomal translocation t(15; 17) is a specific marker of acute promyelocytic leukemia (APL). In this study, molecular cloning of the t(15;17) breakpoint was carried out in a Chinese APL patient. It has been shown that the retinoic acid receptor alpha (RARA) gene, normally located on chromosome 17, was fused with a new transcription unit PML, normally localized on chromosome 15. We have subsequently cloned a portion of the PML gene and generated a panel of probes. A PML gene rearrangement was detected in 33 out of 36 APL cases studied. 24 rearrangements were clustered in a 4.4 kb region, designated here as PML^(bcr1) whereas 9 rearrangements were concentrated in a 6.5 kb region, defining another breakpoint cluster region (PML^(bcr2)). These two types of rearrangement constitute the basis for the heterogeneity of the PML-RARA fusion gene and its possible biological significance remains to be explored.展开更多
Introduction:Acute promyelocytic leukemia(APL)is mostly due to the chromosome translocation t(15;17)(q22;q12),leading to the formation of PML-RARA fusion protein.Some patients carried rare translocation involving RARA...Introduction:Acute promyelocytic leukemia(APL)is mostly due to the chromosome translocation t(15;17)(q22;q12),leading to the formation of PML-RARA fusion protein.Some patients carried rare translocation involving RARA gene,who were called variant APL caused by RAR family(RARA,RARB,and RARG)and partner genes.STAT5b-RARA was a rare type of molecular genetic abnormality with unfavorable prognosis which have been reported in only 18 cases in variant APL.Knowledge of STAT5b-RARA(+)APL treatment is still limited.Case report:We presented a 38-year-old female variant APL case,who was STAT5b-RARA positive detected by reverse transcription polymerase chain reaction.The patient failed to respond after four-drug combined induction chemotherapy:idarubicin,cytarabine,all trans retinoic acid,and arsenic trioxide(As 2 O 3).Then,the patient was re-induced with azacytidine,but still failed to achieve complete remission(CR).Next,she was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR.Later,the patient received hematopoietic stem cell transplantation after 4 cycles of consolidation therapy.Conclusion:Venetoclax combining with homoharringtonine and cytarabine has been used as the salvage therapy in the STAT5b-RARA positive APL successfully.展开更多
目的应用蛋白质组学方法筛选人急性早幼粒细胞白血病(APL)维甲酸敏感细胞株(NB4细胞株)和维甲酸耐药细胞株(NB4-R1细胞株)的耐药相关蛋白。方法利用双向凝胶电泳技术检测,比较NB4和NB4-R1细胞株的总蛋白,建立二维凝胶电泳(two-dimension...目的应用蛋白质组学方法筛选人急性早幼粒细胞白血病(APL)维甲酸敏感细胞株(NB4细胞株)和维甲酸耐药细胞株(NB4-R1细胞株)的耐药相关蛋白。方法利用双向凝胶电泳技术检测,比较NB4和NB4-R1细胞株的总蛋白,建立二维凝胶电泳(two-dimensional gel electrophoresis,2-DE)图谱。从多个差异蛋白质点中选择出2个在NB4-R1细胞株中表达明显上调的蛋白质点进行MALDI-TOF-MS生物质谱分析,并用Mascot软件在SwissProt和NCBInr数据库中进行同源比较和分析鉴定。结果确定表达明显上调的两个蛋白质分别为原肌球蛋白(tropomyosin,TM)和丙酮酸激酶(Pyruvate kinase,PK)。结论本研究表明维甲酸耐药细胞中原肌球蛋白和丙酮酸激酶表达上调,提示它们在肿瘤耐药中有重要作用。展开更多
文摘Acute promyelocytic leukemia (APL) represents the first example o f a human cancer successfully treated with a differentiation reducer, all-trans retinoic acid. APL is also characterized by a specific chromosome translocution t (15; 17). In this work, using techniques of molecular biology, we demonstrated that the gene coding for the retinoic acid receptor alpha (RARA), normally located on chromosome 17, was disrupted by the t (15; 17) and fused with the PML gene on chromosome 15. The chromosome 17 breaks were mapped consistently within the second intron of the RARA gene while the chromosome 15 breaks were clustered in two limited regions within the PML gene. Molecular cloning and sequence analysis of part of the PML gene allowed to establish a specific "nested" reverse transcription/polymerase chain reaction (PCR) procedure to characterize the expression patterns of the PML-RARA fusion gene. Different iso forms of the fusion transcripts were discovered which were produced as a result of distinct PML gene rearrangements. The biological activity of the PML-RARA fusion gene and its iso forms should be further explored.
基金Supported by grants from National Natural Science Foundation of China (No. 39870358)Natural Science Foundation of Guangdong Province (No. 2005B50301016).
文摘Objective： To investigate the distribution and clonality of TCR Va subfamily T cells in patients with acute promyelocytic leukemia （APL）. Methods： The complementary determining region 3 （CDR3） of TCR Va 29 subfamily genes in peripheral blood mononuclear cells from 9 APL patients were amplified using RT-PCR. The positive products were further analyzed to identity the clonality of T cells by GeneScan technique. Results： One to seven of TCR Va subfamilies could be detected in peripheral blood T cells from 9 cases with APL, the frequent expression of Va subfamilies predominated in Vα3 and Va19. Clonal expanded T cells could be detected in 8 APL patients, which predominant used Va3, Va26 or Va27 （3 out of 8 cases）. However, almost all Va subfamilies with polyclonal expansion could be detected in peripheral blood T cells from 10 cases of normal individuals. Conclusion： Remarkable skew distribution and clonal expansion of TCR Va subfamilies T cells is the common feature in patients with APL. Clonal expansion of T cells might reflect a response in host to APL cell associated antigen, whether these expanded T cells have the ability for specific cytotoxicity against APL cells, remains an open question.
基金Preject supported by grant from the Chinese Foundation for High Technology (863).
文摘Chromosomal translocation t(15; 17) is a specific marker of acute promyelocytic leukemia (APL). In this study, molecular cloning of the t(15;17) breakpoint was carried out in a Chinese APL patient. It has been shown that the retinoic acid receptor alpha (RARA) gene, normally located on chromosome 17, was fused with a new transcription unit PML, normally localized on chromosome 15. We have subsequently cloned a portion of the PML gene and generated a panel of probes. A PML gene rearrangement was detected in 33 out of 36 APL cases studied. 24 rearrangements were clustered in a 4.4 kb region, designated here as PML^(bcr1) whereas 9 rearrangements were concentrated in a 6.5 kb region, defining another breakpoint cluster region (PML^(bcr2)). These two types of rearrangement constitute the basis for the heterogeneity of the PML-RARA fusion gene and its possible biological significance remains to be explored.
基金The authors would like to appreciate the funding of National Key Research and Development Program of China(2019YFC0840605).
文摘Introduction:Acute promyelocytic leukemia(APL)is mostly due to the chromosome translocation t(15;17)(q22;q12),leading to the formation of PML-RARA fusion protein.Some patients carried rare translocation involving RARA gene,who were called variant APL caused by RAR family(RARA,RARB,and RARG)and partner genes.STAT5b-RARA was a rare type of molecular genetic abnormality with unfavorable prognosis which have been reported in only 18 cases in variant APL.Knowledge of STAT5b-RARA(+)APL treatment is still limited.Case report:We presented a 38-year-old female variant APL case,who was STAT5b-RARA positive detected by reverse transcription polymerase chain reaction.The patient failed to respond after four-drug combined induction chemotherapy:idarubicin,cytarabine,all trans retinoic acid,and arsenic trioxide(As 2 O 3).Then,the patient was re-induced with azacytidine,but still failed to achieve complete remission(CR).Next,she was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR.Later,the patient received hematopoietic stem cell transplantation after 4 cycles of consolidation therapy.Conclusion:Venetoclax combining with homoharringtonine and cytarabine has been used as the salvage therapy in the STAT5b-RARA positive APL successfully.
文摘目的应用蛋白质组学方法筛选人急性早幼粒细胞白血病(APL)维甲酸敏感细胞株(NB4细胞株)和维甲酸耐药细胞株(NB4-R1细胞株)的耐药相关蛋白。方法利用双向凝胶电泳技术检测,比较NB4和NB4-R1细胞株的总蛋白,建立二维凝胶电泳(two-dimensional gel electrophoresis,2-DE)图谱。从多个差异蛋白质点中选择出2个在NB4-R1细胞株中表达明显上调的蛋白质点进行MALDI-TOF-MS生物质谱分析,并用Mascot软件在SwissProt和NCBInr数据库中进行同源比较和分析鉴定。结果确定表达明显上调的两个蛋白质分别为原肌球蛋白(tropomyosin,TM)和丙酮酸激酶(Pyruvate kinase,PK)。结论本研究表明维甲酸耐药细胞中原肌球蛋白和丙酮酸激酶表达上调,提示它们在肿瘤耐药中有重要作用。
