Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia

By K. Roberts, Ryan D. Morin, Jinghui Zhang, M. Hirst, Yongjun Zhao, X. Su, Shann-Ching Chen, D. Payne-Turner, Michelle L. Churchman, R. Harvey and 39 more. Cancer Cell, 2012

712 citations recorded by the source corpus.

SUMMARY Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL, and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2 and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2 negative regulator LNK. Importantly, several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.

Subfields: Hematology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/5ecc13850752cd3bc3523e331d02fc056cdd69a6

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Citations in the corpus

MOSAIK: A Hash-Based Algorithm for Accurate Next-Generation Sequencing Short-Read Mapping (2013, methodology): “In addition to the 1000 Genomes Project, MOSAIK is widely used for other human clinical genome studies, such as human cancer studies (Su et al. 2012; Kathryn G Roberts et al. 2012; Lin et al. 2012; Wang et al. 2011; Chung et al. 2011; Goya et al. 2010).”
ABySS 2.0: resource-efficient assembly of large genomes using a Bloom filter (2016, neutral): “Although this enabling technology found applications in many large cancer cohort studies (Yip et al. 2011; Roberts et al. 2012; Pugh et al. 2013; Ley et al. 2013; Morin et al. 2013), its large memory footprint constituted a substantial bottleneck.”
A Comprehensive Review (2017, neutral): “This is followed by complete whole-genome and whole-exome sequencing to identify the full repertoire of kinase alterations, performed by the end of remission induction.(23,33) As diagnostic algorithms provide valuable guidance in the evaluation of BCR-ABL1–like cases, we hereby propose a novel diagn”
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. (2016, neutral): “Common features of BCR-ABL1–like ALL include translocations involving other tyrosine kinases, or alternatively translocations involving either the cytokine receptor-like factor 2 (CRLF2) or, less commonly, rearrangements leading to truncation and activation of the erythropoietin receptor (EPOR).(122”