Artikel ; Online: ZMIZ1::ABL1 Fusion: An Uncommon Molecular Event With Clinical Implications in Pediatric Cancer.
Archives of pathology & laboratory medicine
2024
Abstract: ... Karyotype analysis of the bone marrow demonstrated a complex karyotype with, most notably, a t(9;10)(q34.1 ... as a consequence of t(9;10)(q34.1;q22). Three-dimensional modeling of the mutant ZMIZ1::ABL1 fusion protein ... active conformation.: Conclusions.—: The t(9;10) translocation resulting in ZMIZ1::ABL1 fusion ...
Abstract | 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. Three-dimensional 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. |
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Sprache | Englisch |
Erscheinungsdatum | 2024-05-16 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article |
ZDB-ID | 194119-7 |
ISSN | 1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985 |
ISSN (online) | 1543-2165 |
ISSN | 0363-0153 ; 0096-8528 ; 0003-9985 |
DOI | 10.5858/arpa.2024-0082-OA |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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