Project description:The Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. In this study, the tyrosine kinase inhibitor imatinib was used for pharmacological inhibition of BCR-ABL1. Gene expression profiles of Ph+ ALL cell lines were analyzed in response to imatinib treatment.
Project description:This data set consists of pediatric acute lymphoblastic leukemia (ALL) primary bone marrow biopsies from the BC Children's Hospital BioBank, pediatric ALL cell lines, non-cancer bone marrow biopsies, and few ALL PDX. All files are DIA and searched by Spectronaut with a spectral library.
Project description:Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) is driven by genetic alterations that induce constitutive kinase signaling and is associated with chemoresistance and high relapse risk in children and adults. Preclinical studies in the most common CRLF2-rearranged/JAK pathway-activated Ph-like ALL subtype suggest incomplete oncogene addiction and partial response to tyrosine kinase inhibitor (TKI)-based therapies, highlighting a need to elucidate alternative biologic dependencies and therapeutic vulnerabilities, although the ABL-class Ph-like ALL subtype may be preferentially TKI-sensitive. Using bulk and single-cell multiomics analyses, we profiled residual cells from Ph-like ALL xenograft models treated in vivo with inhibitors to identify mechanisms of potential therapeutic escape. We identified a specific MYC dependency in Ph-like ALL and defined a leukemia cell subpopulation with senescence-associated stem cell-like features regulated by AP-1 transcription factors. This dormant ALL subpopulation could be eradicated by dual pharmacologic inhibition of JAK/STAT and BCL-2, providing mechanistic rationale for alternative therapeutic approaches.
Project description:The Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. In this study, the tyrosine kinase inhibitor imatinib was used for pharmacological inhibition of BCR-ABL1. Gene expression profiles of Ph+ ALL cell lines were analyzed in response to imatinib treatment. Four Ph+ ALL cell lines (BV-173, NALM-1, SUP-B15, and TOM1) were either treated with 10µM STI571 (Imatinib) for 16 hours or cultured in absence of STI571.
Project description:Mixed-lineage leukemias represent about 3-5% of acute leukemias occurring in patients of all ages and comprise several different subtypes (biphenotypic, bilineal, and lineage switch). The optimal therapeutic approach to these cases, especially in pediatric patients, has not been defined. We used microarrays to detail the gene expression of pediatric patients with biophenotypic leukemia. Keywords: Patient sample accumulation