TARGET Acute Lymphoblastic Leukemia (ALL)
Program Description
GDC studies: TARGET-ALL-P1, TARGET-ALL-P2, and TARGET-ALL-P3
The TARGET Acute Lymphoblastic Leukemia projects uses comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of hard-to-treat childhood cancers. Acute lymphoblastic leukemia (ALL) is a cancer of white blood cells, the cells in the body that normally fight infection.
The TARGET ALL Pilot project (TARGET ALL Phase I) produced comprehensive genomic profiles of nearly 200 high-risk, clinically annotated, B-cell ALL patient cases from Children’s Oncology Group (COG) for molecular alterations. Each fully characterized TARGET ALL case includes data from primary tumor sample collected at diagnosis and case-matched tissue sample extracted at the time of remission. Additional cases with partial molecular characterization and/or sequencing data are available to the research community.
In the TARGET ALL expansion effort (TARGET ALL Phase II), TARGET investigators analyzed tumors from pediatric patients, most who experienced an early bone marrow relapse (within 4 years of initial diagnosis), to identify new therapeutic approaches and/or biomarkers that correlate with poor clinical outcome to treat childhood pre-cursor B-cell ALL. The TARGET ALL Phase II project has produced comprehensive genomic profiles of nearly 200 relapse-enriched, clinically annotated patient cases in the discovery dataset. This cohort includes more than 100 patients with adequate relapse specimens to study as trios (primary tumor collected at diagnosis, case-matched sample collected at remission, and relapse samples when available). Each fully-characterized TARGET ALL case includes data from nucleic acid samples extracted from peripheral blood or bone marrow tissues
The ALL project team members (like other TARGET researchers) have generated data in two phases: Discovery and Validation. Visit the TARGET Research page to learn more.
The latest TARGET ALL study (TARGET ALL Phase III) focused on acute leukemias of ambiguous lineage (ALAL). Leukemia is a cancer of blood cells and can arise within distinct lineages, either lymphoid or myeloid. On occasion, patients present with an acute leukemia for which a specific lineage cannot be clearly determined. These cases are classified as acute leukemias of ambiguous lineage (ALAL), and they account for less than 4% of all acute leukemias across age groups.
TARGET investigators at St. Jude Children’s Research Hospital led an effort to better understand acute leukemias of ambiguous lineage (ALAL), and the TARGET initiative contributed to this key study by generating whole genomic sequencing (WGS) and some transcriptome (mRNA-seq and miRNA-seq) profiles of ~50 ALAL cases in the TARGET ALL Phase III effort.
Publications
- Alexander TB, Gu Z, Iacobucci I, et al. (2018). The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature. 562(7727):373-379. (PMID: 30209392) View PubMed abstract View PubMed abstract View Publication Information And Supplementary Files
- Liu Y, Easton J, Shao Y, et al. (2017). The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 49(8):1211-1218. (PMID: 28671688) View PubMed abstract View Publication Information And Supplementary Files
- Ma X, Edmonson M, Yergeau D, et al. (2015) Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia. Nat Commun. 19;6:6604. (PMID: 25790293) View PubMed abstract View Publication Information And Supplementary Files
- Roberts KG, Li Y, Payne-Turner D, et al. (2014) Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 11;371(11):1005-15. (PMID: 25207766) View PubMed abstract View Publication Information And Supplementary Files
- Mullighan CG. (2012) The molecular genetic makeup of acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2012:389-96. (PMID: 23233609) View PubMed abstract View Publication Information And Supplementary Files
- Loh ML, Zhang J, Harvey RC, et al. (2012) Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project. Blood 121(3):485-8. (PMID: 23212523) View PubMed abstract View Publication Information And Supplementary Files
- Roberts K, Morin R, Zhang J, et al. (2012) Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell 22(2):153-66. (PMID: 22897847) View PubMed abstract View Publication Information And Supplementary Files
- Zhang J, Mullighan CG, Harvey RC, et al. (2011) Key pathways are frequently mutated in high risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood 118(11): 3080-7. (PMID: 21680795). View PubMed abstract View Publication Information And Supplementary Files
- Harvey RC, Mullighan CG, Wang X, et al. (2010) Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome. Blood 116(23):4874-4884. (PMID: 20699438). View PubMed abstract View Publication Information And Supplementary Files
- Harvey RC, Mullighan CG, Chen IM, et al. (2010) Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Blood 115(26): 5312-5321. (PMID: 20139093). View PubMed abstract View Publication Information And Supplementary Files
- Kang H, Chen IM, Wilson CS, et al. (2009) Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Blood 115(7): 1394-1405. (PMID: 19880498). View PubMed abstract. View Publication Information And Supplementary Files
- Mullighan CG, Zhang J, Harvey RC, et al. (2009) JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA 106(23):9414-9418. (PMID: 19470474). View PubMed abstract View Publication Information And Supplementary Files
- Mullighan CG, Su X, Zhang J, et al. (2009) Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med 360(5):470-480. (PMID: 19129520). View PubMed abstract View Publication Information And Supplementary Files