Unusual PDGFRB fusion reveals novel mechanism of kinase activation in Ph-like B-ALL.
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ABSTRACT:
SUBMITTER: Sadras T
PROVIDER: S-EPMC10079538 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
Publications
Unusual PDGFRB fusion reveals novel mechanism of kinase activation in Ph-like B-ALL.
Sadras Teresa T Jalud Fatimah B FB Kosasih Hansen J HJ Horne Christopher R CR Brown Lauren M LM El-Kamand Sam S de Bock Charles E CE McAloney Lachlan L Ng Ashley P AP Davidson Nadia M NM Ludlow Louise E A LEA Oshlack Alicia A Cowley Mark J MJ Khaw Seong L SL Murphy James M JM Ekert Paul G PG
Leukemia 20230221 4
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Project description:Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a distinct subtype of B-ALL, exhibiting a kinase-activated gene expression profile similar to Philadelphia chromosome-positive (Ph+) ALL, yet lacking the BCR::ABL fusion. Despite the identification of numerous genetic aberrations and chromosomal rearrangements, particularly those involving the ABL-class or CRLF2/JAK pathways, as drivers and therapeutic targets, the genetic diversity and underlying pathogenic mechanisms of Ph-like ALL remain incompletely understood, posing challenges for diagnosis and treatment. Here, we identified a novel JAK2 fusion, ZBTB5::JAK2, in a Ph-like ALL patient, accompanied by a frequent KRAS12D mutation. Single-cell RNA sequencing (scRNA-seq) analysis suggests that the cell population with both high JAK2 and RAS signals may represent the leukemia stem cells in this patient.
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Project description:The novel ZBTB5::JAK2 fusion gene reveals a new mechanism of kinase activation in Ph-like acute lymphoblastic leukemia
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