ZMIZ1::ABL1 Fusion: An Uncommon Molecular Event With Clinical Implications in Pediatric Cancer.
* Context.--Pediatric B-cell acute lymphoblastic leukemia is genetically and phenotypically heterogeneous, with a genetic landscape including chromosomal translocations that disrupt ABL proto-oncogene 1, non--receptor tyrosine kinase (ABL1). Objective.--To characterize an uncommon chromosomal transl...
| Publicado en: | Archives of Pathology & Laboratory Medicine Vol. 149; no. 2; pp. 159 - 165 |
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| Autores principales: | , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
College of American Pathologists
Feb2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=182777046&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 182777046 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00039985 1FS jtl: Archives of Pathology & Laboratory Medicine issn: 00039985 maglogo: N pubinfo: dt: Feb2025 vid: 149 iid: 2 pid: 2550 pub: College of American Pathologists place: Northfield, Illinois artinfo: ui: 182777046 182777046 182777046 10.5858/arpa.2024-0082-OA 182777046 ppf: 159 ppct: 6 formats: fmt: @attributes: type: P tig: atl: ZMIZ1::ABL1 Fusion: An Uncommon Molecular Event With Clinical Implications in Pediatric Cancer. aug: au: Booth, Kevin T. A. Schulte, Rachael R. Smith, Laurin Hongyu Gao Stohler, Ryan A. Yunlong Liu Reshmi, Shalini C. Vance, Gail H. affil: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis sug: subj: Childhood Neoplasms Chromosome Aberrations Leukemia, Lymphocytic, Acute Familial and Genetic Transcription Factors Human Genetic Screening Karyotyping In Situ Hybridization, Fluorescence Sequence Analysis Models, Structural Molecular Structure Bone Marrow Examination ab: * Context.--Pediatric B-cell acute lymphoblastic leukemia is genetically and phenotypically heterogeneous, with a genetic landscape including chromosomal translocations that disrupt ABL proto-oncogene 1, non--receptor tyrosine kinase (ABL1). Objective.--To characterize an uncommon chromosomal translocation in acute leukemia. Design.--Genetic testing, including karyotype and fluorescence in situ hybridization (FISH) analysis, was used to determine the underlying genetic aberration driving the disorder and to guide disease classification and risk stratification. More-detailed testing using RNA sequencing was performed based on the results from these assays. Threedimensional molecular modeling was used to visualize the impact of aberrant fused transcripts identified by transcriptome profiling. Results.--Karyotype analysis of the bone marrow demonstrated a complex karyotype with, most notably, a t(9;10)(q34.1;q22) translocation. ABL1 break-apart probe FISH findings supported ABL1 disruption. Bone marrow transcriptome analysis revealed mutant ZMIZ1::ABL1 (ZMIZ1, zinc finger MIZ-type containing 1) fusion transcripts as a consequence of t(9;10)(q34.1;q22). Three-dimensional modeling of the mutant ZMIZ1::ABL1 fusion protein confirmed an altered ABL1 protein structure compared to that of the wild type, suggesting a constitutively active conformation. Conclusions.--The t(9;10) translocation resulting in ZMIZ1::ABL1 fusion transcripts is an uncommon form of BCR::ABL1-like (BCR, BCR activator of RhoGEF and GTPase) acute lymphoblastic leukemia. Although the karyotype was complex, identifying the t(9;10)(q34.1; q22) translocation, ABL1 disruption, and ZMIZ1::ABL1 transcript enabled effective ABL1-targeted treatment. Our data support the use of tyrosine kinase inhibitors to treat ZMIZ1::ABL1-derived B-cell acute lymphoblastic leukemia. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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