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TARGET’s Study of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a cancer that originates in the bone marrow from immature white blood cells known as myeloblasts. About 25% of all children with leukemia have AML. Although survival rates have increased since the 1970s, approximately half of all childhood AML cases relapse despite intensive treatment. Additional therapies following relapse are often unsuccessful and can be especially difficult and damaging for children. These patients would clearly benefit from targeted therapeutic approaches.

The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) AML projects elucidate comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of high-risk or hard-to-treat childhood cancers. Through comprehensive genome-wide characterization, TARGET researchers are identifying the genetic and epigenetic alterations of relapsed disease. The ultimate goal is to translate their discoveries into novel treatments that will improve outcomes for children with AML. Read more about pediatric AML and current treatment strategies.

TARGET’s AML Project

TARGET investigators are analyzing tumors from pediatric patients, many who have relapsed, to identify biomarkers that correlate with poor clinical outcome or new therapeutic approaches to treat childhood AML. The tissues used in this study were collected from patients enrolled in Children's Oncology Group (COG) biology studies and clinical trials.

The TARGET AML project has produced comprehensive genomic profiles of nearly 200 relapse-enriched, clinically annotated patient cases in the discovery data set. This cohort includes ~100 patients with adequate relapse specimens to study as trios (see three sample types below). Each AML case includes data from nucleic acid samples extracted from peripheral blood or bone marrow tissues as follows:

  • primary tumor sample collected at diagnosis
  • case-matched tissue sample collected at remission (<5% blasts detected following standard induction therapy)
  • relapsed tumor sample (case-matched) when available; ~50% cases have third sample (those cases are considered a “trio”)
  • additional cases with partial molecular characterization and/or sequencing data are available to the research community

Tissues and clinical data used for the TARGET AML project were obtained from patients enrolled on biology studies and clinical trials managed through COG. Patient samples with full characterization were chosen based on the following criteria:

  • patients achieved a remission following a standard two rounds of induction therapy (fewer than 5% blasts)
  • bone marrow and peripheral blood blast counts of >50% in tumor specimens
  • adequate amount of high-quality nucleic acids for comprehensive genomic profiling
  • three or fewer clinically-relevant cytogenetic findings (majority of cases)

Some mutations identified in the relapse-enriched discovery cohort, along with some previously published variants in adult AML, were further analyzed in an additional validation cohort of 600-plus cases. The TARGET AML project team employed targeted capture sequencing to look at the presence and frequency of alterations in 400 gene variants. This validation effort was performed in an unbiased cohort that was randomly selected from patients enrolled on a single COG protocol, which allowed for determination of the frequency of these changes across a broader spectrum of AML subtypes.

Children with AML whose disease is refractory to standard induction chemotherapy therapy or who experience relapse after initial response have poor outcomes. TARGET investigators sequenced and analyzed microRNA to identify dysregulated genes and assess the utility of microRNA signature for improved outcome prediction. 

View AML experimental protocols.

Access AML data at the Genomic Data Commons.

TARGET’s AML Induction Failure Project (AML-IF)

Some AML patients experience something known as an “induction failure.” Upon diagnosis, AML patients without high-risk genetic markers undergo the primary induction phase: standard chemotherapy regimen to eliminate most cancer cells and induce a remission state. Successful treatment reduces the percentage of myeloblasts (immature white blood cells) detected in the patient to less than 15%. Patients with induction failures are those with greater than 15% myeloblasts. Currently, these patients have few clinical options for further treatment.

The TARGET AML Induction Failure (AML-IF) subproject has produced comprehensive genomic profiles of 30 clinically annotated patient cases. Each fully characterized case consists of data generated from nucleic acid samples extracted from case-matched tumor and normal tissues as follows:

  • primary tumor sample collected at diagnosis
  • control fibroblast sample grown from the patient’s bone marrow (case-matched)
  • tumor obtained at the end of induction phase of treatment (two rounds)

Tissues and clinical data used for the TARGET AML-IF project were obtained from patients enrolled on biology studies and clinical trials managed through COG. Patient samples with full characterization were chosen based on the following criteria:

  • patients were not in remission following a standard two rounds of induction therapy (>15% blasts)
  • adequate amount of high-quality nucleic acids for comprehensive genomic profiling

View AML-IF experimental protocols.

Access AML data at the Genomic Data Commons.

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