Identification of Fusion Genes in Pediatric Relapsed AML: A Preliminary Finding
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Event Abstract Back to Event Identification of fusion genes in pediatric relapsed AML: a preliminary finding Nadiah Abu1, 2, Siti Hawa Osman2, Habsah Aziz2, Hamidah Alias3 and Rahman Jamal2* 1 National University of Malaysia, Malaysia 2 UKM Medical Molecular Biology Institute (UMBI), Malaysia 3 Department of Paediatric, Faculty of Medicine, Universiti Kebangsaan Malaysia, Malaysia Background Pediatric Acute Myeloid Leukemia (AML) is a highly complex and heterogenous disease. To date, the mechanisms of its regulatory network, particularly during relapse, have not been elucidated. One of the causes of its pathogenesis is through chromosomal rearrangements, which may result in fusion genes and transcripts. The pattern of expression of fusion genes in relapsed AML is unclear, especially as predictive biomarkers for response or relapse. The best approach is to profile the patients’ cells at diagnosis, remission and relapse. Methods Total RNA was extracted from the bone-marrow derived mononuclear cells of three pediatric AML patients at different stages; diagnosis, remission and relapse. One patient (PAML1) had a normal karyotype, while the other two patients (PAML2 and PAML3) were positive for the t(8 t(8;21) (q;22 q;22) translocation. We performed deep, paired-end RNA sequencing on these AML trios. Putative fusion transcripts were identified and prioritized using the SOAPFuse algorithm. Further visualization of the fusion genes was conducted using Circosplot. Results PAML1 had several novel fusion transcripts, among which, the fusion transcript NTUM2A-AS1>>MINPP1 was persistent at all three stages of diagnosis, remission and relapse. Commonly reported fusion genes involving the MLL gene (MLL>>MLLT4) were also identified in the diagnosis and the relapsed stages. In PAML2, there were no persistent fusion transcripts identified in all three stages. However, as predicted, the RUNX1>>RUNXT1 fusion transcripts were detected in the diagnosis stage and later, reappeared in the relapsed stage. This was also observed for the RRN3P3>>DARS fusion gene. In PAML3, the fusion gene PARP6-JHD1MD persisted in all three stages. Similarly, the RUNX1>>RUNXT1 fusion genes were also detected in PAML3. Interestingly, the fusion gene C15orf57>>CBX3 was found to be expressed in the relapsed stage of all three samples. However, no common fusion genes were detected in the diagnosis and remission stage of all three samples. Conclusion Based on our preliminary findings, fusion genes are selectively expressed at different stages of the disease and in different patients. However, further validation as well as understanding the true biological function of the fusion genes should be investigated. This should be further correlated with the respective gene expression profile, as well as its mutational status. Acknowledgements FRGS/1/2015/SKK08/UKM/03/2 Keywords: Pediatric AML, fusion gene, RNA-Seq, relapse, biomarker, Transcriptome Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Oral Presentation Topic: Metabolic diseases Citation: Abu N, Osman S, Aziz H, Alias H and Jamal R (2019). Identification of fusion genes in pediatric relapsed AML: a preliminary finding. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00144 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Nov 2018; Published Online: 17 Jan 2019. * Correspondence: Prof. Rahman Jamal, UKM Medical Molecular Biology Institute (UMBI), Kuala Lumpur, Malaysia, rahmanj@ppukm.ukm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Nadiah Abu Siti Hawa Osman Habsah Aziz Hamidah Alias Rahman Jamal Google Nadiah Abu Siti Hawa Osman Habsah Aziz Hamidah Alias Rahman Jamal Google Scholar Nadiah Abu Siti Hawa Osman Habsah Aziz Hamidah Alias Rahman Jamal PubMed Nadiah Abu Siti Hawa Osman Habsah Aziz Hamidah Alias Rahman Jamal Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.Keywords:
Fusion transcript
Objective To investigate the value of interphase fluorescence in situ hybridization(FISH)technique and the detection of fusion gene in the diagnosis of acute myeloid leukemia(AML)M2 and M3 Methods FISH was used to detect the AML1/ETO fusion gene and/or PML/RARα fusion gene in incipient cases including 9 AML-M2, 12 AML-M3 and 10 AML undetermined as AML-M2 or AML-M3 primarily diagnosed by routine morphology though bone marrow,cytochemical staining and immunophenotyping,which can help diagnose and guide clinical therapy.Results 4 of 9 AML-M2 cases were AML1/ETO positive.Among 12 AML-M3 cases,10 were PML/RARα positive.1 case was detected AML1/ETO fusion gene.In 10 untonfirmed M3 or M2,3 case8 showed AML1/ETO,5 showed PMIJRARot fusion gene and the rest showed neither of the genes.Conclusion As a new technique of the molecular genetics,FISH is accurate, rapid and efficient.It would be of significance not only at diagnosis of AML,but also for subsequent clinical decision-making.
Key words:
Leukemia,cytic,acute; In situ hybridization,fluorescence; AML1/ETO fusion gene; PML/RARα fusion gene
Immunophenotyping
Interphase
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A new unusual translocation t (19p+; 22q-) was detected in a 31-year-old female with Philadelphia cromosome (Ph1) positive chronic myeloid leukemia (CML). This translocation has apparently not been reported in the literature concerning the Philadelphia chromosome.
Philadelphia chromosome
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To investigate the clinical and laboratory characteristics of four acute myeloid leukemia with t(3;3) translocation.Bone marrow cell chromosome karyotype analysis were carried out with direct method and short-term culture and R-banding technique.Four AML patients with t(3;3) translocation were identified. They did not obtain complete remission after chemotherapy and the median survival time was 4.5 months.t(3;3) translocation is a rare chromosome abnormality, which has mostly been found in myeloid leukemia and the prognosis of these patients is poor.
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Chromosome abnormality
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The authors report their observations on acute myeloid leukemias associated with the 8;21 translocation. Two cases have less than the required percentage of blasts for the cytological diagnosis of acute myeloid leukemia. In one case, the 8;21 translocation is superimposed on a constitutional trisomy 21. Conclusions from the 4th International Workshop on chromosomes in leukemia are highlighted, as well as certain new data relative to the biology of acute myeloid leukemias.
Trisomy
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Event Abstract Back to Event Identification of fusion genes in pediatric relapsed AML: a preliminary finding Nadiah Abu1, 2, Siti Hawa Osman2, Habsah Aziz2, Hamidah Alias3 and Rahman Jamal2* 1 National University of Malaysia, Malaysia 2 UKM Medical Molecular Biology Institute (UMBI), Malaysia 3 Department of Paediatric, Faculty of Medicine, Universiti Kebangsaan Malaysia, Malaysia Background Pediatric Acute Myeloid Leukemia (AML) is a highly complex and heterogenous disease. To date, the mechanisms of its regulatory network, particularly during relapse, have not been elucidated. One of the causes of its pathogenesis is through chromosomal rearrangements, which may result in fusion genes and transcripts. The pattern of expression of fusion genes in relapsed AML is unclear, especially as predictive biomarkers for response or relapse. The best approach is to profile the patients’ cells at diagnosis, remission and relapse. Methods Total RNA was extracted from the bone-marrow derived mononuclear cells of three pediatric AML patients at different stages; diagnosis, remission and relapse. One patient (PAML1) had a normal karyotype, while the other two patients (PAML2 and PAML3) were positive for the t(8 t(8;21) (q;22 q;22) translocation. We performed deep, paired-end RNA sequencing on these AML trios. Putative fusion transcripts were identified and prioritized using the SOAPFuse algorithm. Further visualization of the fusion genes was conducted using Circosplot. Results PAML1 had several novel fusion transcripts, among which, the fusion transcript NTUM2A-AS1>>MINPP1 was persistent at all three stages of diagnosis, remission and relapse. Commonly reported fusion genes involving the MLL gene (MLL>>MLLT4) were also identified in the diagnosis and the relapsed stages. In PAML2, there were no persistent fusion transcripts identified in all three stages. However, as predicted, the RUNX1>>RUNXT1 fusion transcripts were detected in the diagnosis stage and later, reappeared in the relapsed stage. This was also observed for the RRN3P3>>DARS fusion gene. In PAML3, the fusion gene PARP6-JHD1MD persisted in all three stages. Similarly, the RUNX1>>RUNXT1 fusion genes were also detected in PAML3. Interestingly, the fusion gene C15orf57>>CBX3 was found to be expressed in the relapsed stage of all three samples. However, no common fusion genes were detected in the diagnosis and remission stage of all three samples. Conclusion Based on our preliminary findings, fusion genes are selectively expressed at different stages of the disease and in different patients. However, further validation as well as understanding the true biological function of the fusion genes should be investigated. This should be further correlated with the respective gene expression profile, as well as its mutational status. Acknowledgements FRGS/1/2015/SKK08/UKM/03/2 Keywords: Pediatric AML, fusion gene, RNA-Seq, relapse, biomarker, Transcriptome Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Oral Presentation Topic: Metabolic diseases Citation: Abu N, Osman S, Aziz H, Alias H and Jamal R (2019). Identification of fusion genes in pediatric relapsed AML: a preliminary finding. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00144 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Nov 2018; Published Online: 17 Jan 2019. * Correspondence: Prof. Rahman Jamal, UKM Medical Molecular Biology Institute (UMBI), Kuala Lumpur, Malaysia, rahmanj@ppukm.ukm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Nadiah Abu Siti Hawa Osman Habsah Aziz Hamidah Alias Rahman Jamal Google Nadiah Abu Siti Hawa Osman Habsah Aziz Hamidah Alias Rahman Jamal Google Scholar Nadiah Abu Siti Hawa Osman Habsah Aziz Hamidah Alias Rahman Jamal PubMed Nadiah Abu Siti Hawa Osman Habsah Aziz Hamidah Alias Rahman Jamal Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.
Fusion transcript
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Lineage (genetic)
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Objective To investigate the value of diagnosis and prognostic evaluation according to detect the expression of bcr/abl fusion gene in chronic myeloid leukemia by real-time quatitative PCR.Methods To use the real-time PCR to detect the expression of bcr/abl fusion gene of 39 cases chronic myeloid leukemia and 20 cases others hematological diseases.Results Marrow and peripheral blasts showed significant corrilation with the copy of bcr/abl fusion gene.Bcr/abl fusion gene expression level of newly diagnosis chronic myeloid leukemia increased significantly.After the treatment of hydroxycarbamide±interferon,the expression level of the gene decreased markedly.The patients of recurrence or acceleration phase can be found ahead of 2-4 months By the therapy of Glevec or explantation,the most of the fusion gene turned negative.Conclusion The detection of bcr/abl fusion gene is an important way to diagnose chronic myeloid leukemia,and can be a decisive index of treatment and prognostic evaluation.
ABL
breakpoint cluster region
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In myxoid and round cell liposarcomas, a specific chromosomal translocation [(12;16)(q13;p11)] results in the expression of chimeric fusion transcripts encompassing parts of the FUS gene (16p11) at their 5' ends and the CHOP gene (12q13) at their 3' ends. Using a reverse transcription-PCR protocol, we determined the prevalence of FUS-CHOP fusion transcripts in a series of liposarcoma samples. Fusion transcripts were detected in 13 of 30 biopsy samples from soft tissue liposarcomas. Expression of fusion transcripts was not restricted to myxoid and round cell liposarcomas, as suggested previously; it was also detected in 1 of 3 well-differentiated and 4 of 14 pleomorphic liposarcomas. Sequence analysis revealed four different FUS-CHOP fusion transcript variants, two of which have not been described before. Furthermore, using FUS-CHOP fusion transcripts as targets in reverse transcription-PCR assays, we detected disseminated tumor cells in peripheral blood or bone marrow in 3 of 5 patients undergoing surgery for soft tissue liposarcoma.
Fusion transcript
Myxoid liposarcoma
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Molecular monitoring of BCR—ABL1 transcript levels using quantitative polymerase chain reaction is an essential part of the modern management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Establishing the diagnostic BCR—ABL1 fusion transcript is necessary in order to select appropriate primers and probes for such monitoring. A case is described in which quantitative polymerase chain reaction failed to detect the presence of BCR—ABL1 fusion transcript in a Philadelphia chromosome-positive chronic myeloid leukemia patient. Further investigation demonstrated a novel in-frame BCR—ABL1 fusion transcript with a breakpoint in BCR exon 13 and insertion of a sequence of ABL1 intron 1, therefore enabling subsequent molecular monitoring. This case highlights the requirement for characterization of the BCR—ABL1 transcript type at chronic myeloid leukemia diagnosis. Issues concerning standardized methodological approaches and interpretation of transcript levels in such rare cases are discussed.
breakpoint cluster region
Fusion transcript
ABL
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