ID
45173
Description
Principal Investigator: James R. Downing, MD, Dept. of Pathology, St. Jude Children' Research Hospital, Memphis, TN, USA MeSH: Acute Megakaryoblastic Leukemia,Acute Myeloid Leukemia https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000413 High resolution analysis of DNA copy number abnormalities and loss-of-heterozygosity on acute myeloblastic leukemia samples utilizing SNP arrays has demonstrated that in contrast to pediatric ALL, de novo AML is characterized by a very low burden of genomic alterations (Radtke, et al., PNAS, 2009). Samples for this study represented a cross-section of the different subtypes of pediatric AML. The only AML subtype that was an outlier from the above observations was acute megakaryocytic leukemia (AML FAB-M7), with the majority of these cases being characterized by complex chromosomal rearrangements and a high number of copy number alterations. To more fully define the genomic landscape of this subtype, we performed transcriptome sequence analysis on 14 pediatric FAB-M7 cases and mutation recurrence screening in a panel of 62 adult and pediatric AML FAB-M7 samples using the Illumina platform. Our results identified chromosomal rearrangements resulting in the expression of novel fusion transcripts in 11/14 cases. Remarkably, in 7/14 cases we detected an inversion on chromosome 16 that results in the juxtaposition of the CBFA2T3 gene next to the GLIS2 gene resulting in a CBFA2T3-GLIS2 chimeric gene that encoded an in frame fusion protein. This fusion led to the acquisition or preservation of self-renewal in colony forming assays, providing functional evidence for a role in leukemogenesis. In addition to novel chimeric transcripts, we found mutations in genes previously identified to play a role in megakaryoblastic leukemia that carry a proliferative advantage to the cell, such as JAK2 and MPL. These data demonstrate that AML FAB-M7 is characterized by cooperating Class I and Class II mutations leading to leukemogenesis.
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Versions (2)
- 8/22/22 8/22/22 - Niko Möller-Grell
- 10/12/22 10/12/22 - Adrian Schulz
Copyright Holder
James R. Downing, MD, Dept. of Pathology, St. Jude Children' Research Hospital, Memphis, TN, USA
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October 12, 2022
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License
Creative Commons BY 4.0
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dbGaP phs000413 Transcriptome Sequencing of Pediatric AML FAB-M7
Sample ID and GEO accession ID of participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, subject source, subject source ID, and affection status of participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- Sample ID, subject ID, sample source, sample source ID, and sample use variables obtained from participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- Sample ID, body site where sample was collected, analyte type of samples, tumor status, histological type of samples, and primary tumor location obtained from participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- Subject ID, age at diagnosis, ethnicity, gender, relapse and vital status, if patient receive a bone marrow transplant, primary treatment protocol, disease code, genetic lesions, characteristic of specimen including tumor purity, type of specimen, and tissue site where from the specimen was obtained from participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- Sample ID and GEO accession ID of participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
Similar models
Sample ID and GEO accession ID of participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, subject source, subject source ID, and affection status of participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- Sample ID, subject ID, sample source, sample source ID, and sample use variables obtained from participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- Sample ID, body site where sample was collected, analyte type of samples, tumor status, histological type of samples, and primary tumor location obtained from participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- Subject ID, age at diagnosis, ethnicity, gender, relapse and vital status, if patient receive a bone marrow transplant, primary treatment protocol, disease code, genetic lesions, characteristic of specimen including tumor purity, type of specimen, and tissue site where from the specimen was obtained from participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
- Sample ID and GEO accession ID of participants with acute myeloblastic leukemia and involved in the "Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing" project.
C3847505 (UMLS CUI [1,2])
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