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
BACKGROUND Chromosome i(17)(q10)abnormality is mainly associated with chronic myeloid leukemia(CML),myelodysplastic syndrome/myeloproliferative tumors(MDS/MPD),and acute myeloid leukemia(AML).The role of i(17)(q10)in ...BACKGROUND Chromosome i(17)(q10)abnormality is mainly associated with chronic myeloid leukemia(CML),myelodysplastic syndrome/myeloproliferative tumors(MDS/MPD),and acute myeloid leukemia(AML).The role of i(17)(q10)in AML is still unknown,the differences between AML and acute promyelocytic leukemia(APL)-like AML with i(17)(q10)need more research.This study aimed to investigate the clinical characteristics and laboratory evidence of 2 AML cases with i(17)(q10),similar to APL phenotype.CASE SUMMARY Both pediatric patients were males;case 1 had newly diagnosed AML,and case 2 showed relapsed tumor after 1 year of drug withdrawal.Bone marrow cell morphology,chromosome karyotype analysis,Fully-instrumented submersible housing test,immunological assays,molecular biological methods,and blood tumor panoramic gene test were performed.All-trans retinoic acid(ATRA)combined with arsenic acid(As2O3)were used in the first course of treatment.Bone marrow was dominated by abnormal promyelocytic granulocytes.Karyotype test revealed i(17)(q10)isochromosome.Immunological phenotype mainly included positive expressions of CD9,CD13,CD33,and CD38.Case 1 suffered intracranial hemorrhage after re-chemotherapy and died on D162.For case 2,on D145 and D265,bone marrow promyelocytic granulocytes accounted for 2%.Flow cytometric residual lesion detection showed no abnormal immunophenotype cells.The copy number of WT1 gene in two cases were 1087 and 1010,respectively,and the expression rates were 55.29% and 59.5%,respectively.CONCLUSION ATRA,As2O3,and chemotherapy may be ineffective in treating APL-like AML with i(17)(q10)but without t(15;17)and PML-RARA fusion gene.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
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 Shaanxi Natural Science Foundation,No.2020SF-004.
文摘BACKGROUND Chromosome i(17)(q10)abnormality is mainly associated with chronic myeloid leukemia(CML),myelodysplastic syndrome/myeloproliferative tumors(MDS/MPD),and acute myeloid leukemia(AML).The role of i(17)(q10)in AML is still unknown,the differences between AML and acute promyelocytic leukemia(APL)-like AML with i(17)(q10)need more research.This study aimed to investigate the clinical characteristics and laboratory evidence of 2 AML cases with i(17)(q10),similar to APL phenotype.CASE SUMMARY Both pediatric patients were males;case 1 had newly diagnosed AML,and case 2 showed relapsed tumor after 1 year of drug withdrawal.Bone marrow cell morphology,chromosome karyotype analysis,Fully-instrumented submersible housing test,immunological assays,molecular biological methods,and blood tumor panoramic gene test were performed.All-trans retinoic acid(ATRA)combined with arsenic acid(As2O3)were used in the first course of treatment.Bone marrow was dominated by abnormal promyelocytic granulocytes.Karyotype test revealed i(17)(q10)isochromosome.Immunological phenotype mainly included positive expressions of CD9,CD13,CD33,and CD38.Case 1 suffered intracranial hemorrhage after re-chemotherapy and died on D162.For case 2,on D145 and D265,bone marrow promyelocytic granulocytes accounted for 2%.Flow cytometric residual lesion detection showed no abnormal immunophenotype cells.The copy number of WT1 gene in two cases were 1087 and 1010,respectively,and the expression rates were 55.29% and 59.5%,respectively.CONCLUSION ATRA,As2O3,and chemotherapy may be ineffective in treating APL-like AML with i(17)(q10)but without t(15;17)and PML-RARA fusion gene.
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.
