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http://purl.uniprot.org/citations/34855461http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34855461http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Increased CD123 surface expression has been associated with high-risk disease characteristics in adult acute myeloid leukemia (AML), but has not been well-characterized in childhood AML. In this study, we defined CD123 expression and associated clinical characteristics in a uniformly treated cohort of pediatric patients with newly diagnosed AML enrolled on the Children's Oncology Group AAML1031 phase III trial (NCT01371981).

Materials and methods

AML blasts within diagnostic bone marrow specimens (n = 1,040) were prospectively analyzed for CD123 protein expression by multidimensional flow cytometry immunophenotyping at a central clinical laboratory. Patients were stratified as low-risk or high-risk on the basis of (1) leukemia-associated cytogenetic and molecular alterations and (2) end-of-induction measurable residual disease levels.

Results

The study population was divided into CD123 expression-based quartiles (n = 260 each) for analysis. Those with highest CD123 expression (quartile 4 [Q4]) had higher prevalence of high-risk KMT2A rearrangements and FLT3-ITD mutations (P < .001 for both) and lower prevalence of low-risk t(8;21), inv(16), and CEBPA mutations (P < .001 for all). Patients in lower CD123 expression quartiles (Q1-3) had similar relapse risk, event-free survival, and overall survival. Conversely, Q4 patients had a significantly higher relapse risk (53% v 39%, P < .001), lower event-free survival (49% v 69%, P < .001), and lower overall survival (32% v 50%, P < .001) in comparison with Q1-3 patients. CD123 maintained independent significance for outcomes when all known contemporary high-risk cytogenetic and molecular markers were incorporated into multivariable Cox regression analysis.

Conclusion

CD123 is strongly associated with disease-relevant cytogenetic and molecular alterations in childhood AML. CD123 is a critical biomarker and promising immunotherapeutic target for children with relapsed or refractory AML, given its prevalent expression and enrichment in patients with high-risk genetic alterations and inferior clinical outcomes with conventional therapy."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.org/dc/terms/identifier"doi:10.1200/jco.21.01595"xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Wang J."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Pardo L."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Alonzo T.A."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Meshinchi S."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Cooper T.M."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Sung L."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Loken M.R."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Kolb E.A."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Aplenc R."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Tasian S.K."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Eidenschink Brodersen L."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/author"Lamble A.J."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/name"J Clin Oncol"xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/pages"252-261"xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/title"CD123 Expression Is Associated With High-Risk Disease Characteristics in Childhood Acute Myeloid Leukemia: A Report From the Children's Oncology Group."xsd:string
http://purl.uniprot.org/citations/34855461http://purl.uniprot.org/core/volume"40"xsd:string
http://purl.uniprot.org/citations/34855461http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/34855461
http://purl.uniprot.org/citations/34855461http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/34855461
http://purl.uniprot.org/uniprot/#_P26951-mappedCitation-34855461http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34855461
http://purl.uniprot.org/uniprot/P26951http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/34855461