Our patient-derived xenografts (PDXs) have been created from a variety of adult and pediatric leukemias at St. Jude Children’s Research Hospital. The PROPEL data portal consists of data generated from these PDXs. As of September 2020, the portal represents samples from six types of leukemias and more than 20 subtypes in the data portal with a variety of samples within different diagnoses.
Acute lymphoblastic leukemia (ALL)
ALL is the commonest childhood tumor and an important cause of morbidity and mortality from leukemia in adults. Studies led by St Jude investigators, with collaborators from the NCI TARGET initiative (https://ocg.cancer.gov/programs/target) and adult cooperative leukemia groups have defined many of the genomic subtypes of B-progenitor and T-lineage ALL and their variation in prevalence according to age. PROPEL contains xenografts for many of these subtypes, including BCR-ABL1-like, DUX4-rearranged, MEF2D-rearranged, NUTM1-rearranged and ZNF384-rearranged ALL, many of which have been used for preclinical therapeutic studies and are luceiferase-marked. Key publications describing the genomic landscape of B-progenitor ALL are PMID 30643249, and for T-ALL, PMID 28671688.
Acute myeloid leukemia (AML)
AML is less common in children than adults, but an important cause of morbidity and mortality. PROPEL has fewer childhood AML samples than ALL, but ongoing efforts are increasing number of samples engrafted, including samples with common pediatric AML-associated abnormalities, including KMT2A rearrangments. Samples of acute erythroleukemia (PMID 30926971) are also included.
Early T-cell precursor leukemia (ETP ALL)
ETP ALL is characterized by leukemic cell expression of cytoplasmic CD3 and CD7, lack of expression of canonical T-ALL markers such as CD1a and CD8, weak or absent expression of CD5, and aberrant expression of myeloid or stem cell markers. ETP ALL was named due to the observed similarity of immunophenotype to the mouse early T cell precursor, the earliest stage of thymic development. Genomic analyses (PMID 25696852) have demonstrated that ETP ALL has a heterogeneous mutational spectrum with frequent mutation of myeloid transcriptional regulators, chromatin modifying genes (particularly those encoding polycomb repressor complex 2) and signaling pathways (Ras, FLT3, JAK-STAT). These analysis have also demonstrated the similarity of human ETP ALL leukemic cells to normal and malignant myeloid stem cells. ETP ALL is thus now considered part of a spectrum of lineage ambiguous leukemias rather than T-ALL.
Mixed phenotype acute leukemia (MPAL)
MPAL represents another subset of lineage ambiguous leukemias that typically simultaneously express myeloid with B- or T-cell markers (thus, B/myeloid or T/myeloid MPAL). Expression of the myeloid marker myeloperoxidase (MPO) commonly distinguishes MPAL from ETP ALL, although these entities otherwise often share similarities in gene expression, immunophenotype and mutational spectra. MPAL is also notable for the intra-sample and temporal lineage plasticity: individual samples often have multiple subpopulations with T/B and/or myeloid features; and the immunophenotype may shift during disease progression to and from MPAL and ETP-ALL/AML, or MPAL and ALL. The conventional definition of MPAL, like ETP ALL is based on flow cytometry rather than genomic features. Recent genomic analyses have begun to elucidate specific subsets of MPAL, some of which transcend MPAL and include immunophenotypically conventional ALL/AML cases (e.g. ZNF384-rearranged B/myeloid MPAL and B-ALL; PMID 30209392). The genomic features of pediatric and adult MPAL differ (e.g. ZNF384 fusions are rare in adult MPAL; PHF6 and DNMT3A mutations are commoner in adult; PMID 29991687). Xenograft and genomic analysis of pediatric MPAL has shown that the lineage plasticity is inherent to tumor cells rather than mutational diversification.
Tumor Types
Tumor Sub-Types
Contain 23 cases with paired Diagnosis-Relapse samples (sequencing pending).