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  • New AML Therapy and Diagnostic

    Abstract Full Text
    JAMA. 2017; 317(21):2157-2157. doi: 10.1001/jama.2017.6304
  • Scientists Identify Genes Critical to Development of Leukemia

    Abstract Full Text
    JAMA. 2016; 315(9):860-860. doi: 10.1001/jama.2016.1486
  • Red-Brown Plaques and Papules in a Patient With Breast Cancer

    Abstract Full Text
    JAMA. 2015; 314(20):2182-2183. doi: 10.1001/jama.2015.10953

    A 55-year-old woman presented with a generalized erythematous maculopapular rash after receiving breast cancer chemotherapy. She was afebrile and had no constitutional symptoms; laboratory evaluation revealed pancytopenia, and a computed tomography scan showed no metastasis. What would you do next?

  • JAMA August 25, 2015

    Figure 3: Day 30 Mutation Clearance Patterns by Patient for 50 Acute Myeloid Leukemia Cases

    AML indicates acute myeloid leukemia; AML-RMG, recurrently mutated AML genes; EFS, event-free survival; VAF, variant allele frequency. Top: bar plots showing the number of mutations assessed at day 30, color coded according to whether they exceeded the day 30 VAF threshold of 2.5%. Mutations that occurred in AML-RMG are labeled with white diamonds. The panel is divided into samples with at least 1 variant with a day 30 VAF of 2.5% or more (left) and samples in which the day 30 VAF for all mutations was less than 2.5% (right). Bottom: key AML genes and pathways, showing patterns of mutations and clearance. aThree cases that received an allogeneic transplant in the first complete remission. Exclusion of these 3 cases from the analysis did not significantly alter the outcome results. bThe median event-free survival of cases with a day 30 VAF of less than 2.5% for all mutations was 17.9 months vs 6.0 months for the cases in which at least 1 variant persisted with a VAF threshold of 2.5% or more (P < .001).
  • JAMA August 25, 2015

    Figure 4: Day 30 Mutation Clearance by Gene for 50 Acute Myeloid Leukemia Cases

    VAF indicates variant allele frequency. Serial VAF measurements demonstrating the clearance patterns of several recurrently mutated acute myeloid leukemia genes in the set of 50 cases. Orange lines indicate a day 30 VAF of 2.5% or more; blue lines indicate a day 30 VAF of less than 2.5%.
  • JAMA August 25, 2015

    Figure 2: Clearance Patterns of Acute Myeloid Leukemia–Associated Mutations Detected by Exome Sequencing

    VAF indicates variant allele frequency. Panels A through D show examples of different patterns of clearance of leukemia-associated mutations after induction therapy in 4 acute myeloid leukemia cases. Key leukemic variants are highlighted by labels and color. All patients had a morphologic complete remission in the approximately day 30 sample (thick gray line shows that blast counts declined to <5% on approximately day 30 for all cases). The patterns include complete clearance of all variants at day 39 that remain undetectable during an extended remission (>1 year) (panel A); incomplete clearance of most variants at day 31, with subsequent return of these mutations at relapse on day 90 (panel B); clearance of subclonal variants at day 32 (panel C) or day 39 (panel D), with persistence of founding clone variants that remain present at relapse (eg, TET2 for panel C and DNMT3A and IDH2 for panel D). Panels E and F, for the 25 samples with follow-up exome sequencing, the clearance patterns of all leukemia-associated variants detected on day 0 are separately shown for patients with an event-free survival of 12 months or less (n = 16, panel E) or more than 12 months (n = 9, panel F).aThe high TET2 VAF levels (75%-90%) in panel C suggest that 1 copy of TET2 was probably deleted in the founding clone of this acute myeloid leukemia sample.
  • Next-Generation Sequencing and Detection of Minimal Residual Disease in Acute Myeloid Leukemia: Ready for Clinical Practice?

    Abstract Full Text
    JAMA. 2015; 314(8):778-780. doi: 10.1001/jama.2015.9452
  • Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia

    Abstract Full Text
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    JAMA. 2015; 314(8):811-822. doi: 10.1001/jama.2015.9643

    This cohort study investigates clearance patterns of somatic mutations in acute myeloid leukemia patients given induction chemotherapy, and associations between those patterns and clinical outcomes.

  • JAMA August 25, 2015

    Figure 5: Association Between Mutation Clearance and Outcomes

    AML indicates acute myeloid leukemia; VAF, variant allele frequency. Data were censored at last contact or at January 21, 2015.
  • JAMA August 25, 2015

    Figure 1: Flowchart Outlining the Selection of Samples and Sequencing Approaches in the Study

    aAML-RMG is a capture reagent consisting of all of the exons of the genes that are currently known to be recurrently mutated in acute myeloid leukemia, based on The Cancer Genome Atlas AML study.bThe only samples with sufficient day 30 DNA for sequencing and assessment of disease clearance (refractory group, 6 patients; R6-12 group, 8 patients; LFR group, 11 patients).cEnhanced exome sequencing is exome capture-based sequencing supplemented with the AML-RMG panel of target genes, to improve coverage of critical regions of the exome. dTargeted Ampliseq is a polymerase chain reaction–based digital sequencing approach that allows for accurate determination of the frequency of specific mutations in acute myeloid leukemia samples.
  • JAMA December 22, 2010

    Figure 4: Association Between Leukemic Stem Cell (LSC) Score and Survival Outcomes in Patients With Normal Karyotype Acute Myeloid Leukemia (AML)

    Stratification of outcomes using this approach is depicted for overall survival in the training set and in one of the validation sets and event-free survival in one of the validation sets. Vertical ticks on curves indicate censored events. Similar results were obtained in the other independent data sets (Table 2 and eFigure 4).
  • Acute Myeloid Leukemia

    Abstract Full Text
    JAMA. 2010; 304(24):2759-2759. doi: 10.1001/jama.302.22.2759
  • Association of a Leukemic Stem Cell Gene Expression Signature With Clinical Outcomes in Acute Myeloid Leukemia

    Abstract Full Text
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    JAMA. 2010; 304(24):2706-2715. doi: 10.1001/jama.2010.1862
  • JAMA December 22, 2010

    Figure 1: Differences in Gene Expression Between LPC- and LSC-Enriched Subpopulations

    Gene expression heat map with each column representing the difference in expression between subpopulations enriched with leukemic stem cells (LSCs) or leukemia progenitor cells (LPCs) isolated from the same patient with acute myeloid leukemia. Hs indicates LSC/LPC profile purified from primary human patient specimen; Mm, corresponding samples from mouse xenografts. A total of 52 unique genes were identified as differentially expressed between LSC and LPC at a 10% false discovery rate (eTable 2), with red indicating higher expression in LSC.
  • JAMA December 22, 2010

    Figure 2: Enrichment Analysis of Relative Expression Between Leukemic Stem Cells (LSCs) and Leukemic Progenitor Cells (LPCs)

    Analysis of 17 119 genes (eTable 2 for gene set definitions). Vertical bars in each of the 6 rows represent genes from each of the indicated gene sets. All nominal P values were less than .001. AML indicates acute myeloid leukemia; FDR, false discovery rate; NES, normalized enrichment score.
  • JAMA December 22, 2010

    Figure 3: Expression of the Leukemic Stem Cell (LSC) Signature Across Cell Subpopulations

    All of the data are from Stanford cases. The boxes span the interquartile range with the median depicted by the thick horizontal bar. Each circle indicates 1 sample. Wilcoxon rank sum test P <.002 for LSC compared with LPC and leukemic blast cells (BLAST). Wilcoxon rank sum test P <.001 for HSC compared with multipotent progenitor (MPP), common myeloid progenitor (CMP), granulocyte-monocyte progenitor (GMP), and megakaryocyte-erythrocyte progenitor (MEP) cells. AML indicates acute myeloid leukemia; LPC, leukemic progenitor cell. Error bars indicate full range.
  • Acute Myeloid Leukemia

    Abstract Full Text
    JAMA. 2009; 301(22):2402-2402. doi: 10.1001/jama.301.22.2402
  • Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission: Systematic Review and Meta-analysis of Prospective Clinical Trials

    Abstract Full Text
    JAMA. 2009; 301(22):2349-2361. doi: 10.1001/jama.2009.813
  • JAMA June 10, 2009

    Figure 3: Overall Survival Benefit of Allogeneic SCT for AML in First Complete Remission

    Black rectangles indicate summary effects estimates (hazard ratios [HRs]) for individual study reports. Sizes of data markers are proportional to the study weights. Error bars indicate 95% confidence intervals (CIs). AML indicates acute myeloid leukemia.
  • JAMA June 10, 2009

    Figure 2: Relapse-Free Survival (RFS) Benefit of Allogeneic SCT for AML in First Complete Remission

    Black rectangles indicate summary effects estimates (hazard ratios [HRs]) for individual study reports. Sizes of data markers are proportional to the study weights. Error bars indicate 95% confidence intervals (CIs). AML indicates acute myeloid leukemia; RFS, relapse-free survival. aStudies only reporting RFS end points.