Publications by authors named "K A Dunsmore"
Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to curing T cell acute lymphoblastic leukemia (T-ALL). While tumor heterogeneity has been implicated in treatment failure, the cellular and genetic factors contributing to resistance and relapse remain unknown. Here we linked tumor subpopulations with clinical outcome, created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic analysis to a diverse cohort of 40 T-ALL cases.
View Article and Find Full Text PDFLimited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children's Oncology Group frontline ALL trials (1996-2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.
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- The study investigates how genetic ancestry affects the biology and survival outcomes of children and young adults with T-cell Acute Lymphoblastic Leukemia (T-ALL), focusing on associations between ancestry, genomic subtypes, and overall and event-free survival rates.
- Among 1309 patients, it was found that T-ALL molecular subtypes differed significantly based on genetic ancestry, with African ancestry patients having a higher prevalence of certain high-risk subtypes.
- The research highlights that existing risk classification models may inaccurately assess patients of African ancestry, suggesting that incorporating genetic ancestry into cancer prognosis and treatment strategies is crucial for more accurate risk stratification.
T-lineage acute lymphoblastic leukaemia (T-ALL) is a high-risk tumour that has eluded comprehensive genomic characterization, which is partly due to the high frequency of noncoding genomic alterations that result in oncogene deregulation. Here we report an integrated analysis of genome and transcriptome sequencing of tumour and remission samples from more than 1,300 uniformly treated children with T-ALL, coupled with epigenomic and single-cell analyses of malignant and normal T cell precursors. This approach identified 15 subtypes with distinct genomic drivers, gene expression patterns, developmental states and outcomes.
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- Defining prognostic factors for T-lymphoblastic lymphoma (T-LL) is complex, as shown in the AALL1231 trial that included children and young adults with T acute lymphoblastic leukemia or T-LL, comparing standard therapy with the addition of bortezomib.
- In the trial, 41% of patients provided bone marrow samples to measure minimal residual disease (MRD) after treatment, revealing that those with MRD levels below 0.1% had a significantly better event-free survival rate (89%) compared to those with MRD at or above 0.1% (64%).
- Cox regression analysis indicated that having MRD levels at or above 0.1%