Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukaemia
Sequencing showed that Ph-like acute lymphoblastic leukaemia, which behaves like Philadelphia-positive disease without the BCR-ABL1 fusion, is driven by a range of kinase-activating alterations, many of them potentially treatable with existing kinase inhibitors.
Overview
Genomic study of 1,725 patients with B-ALL identifying the Ph-like subtype in 15 percent of children and over 25 percent of young adults, with transcriptome and genome sequencing of 154 Ph-like cases revealing ABL-class fusions, CRLF2 rearrangements with JAK mutations, and other JAK-STAT and Ras pathway lesions; cell lines and patient-derived xenografts responded to matching kinase inhibitors.
- Ph-like ALL frequency rises with age: about 10 percent of standard-risk children to over 25 percent of young adults.
- Kinase-activating alterations in 91 percent of Ph-like cases; ABL-class fusions in about 13 percent.
Screening for Ph-like ALL and its underlying kinase lesion is now part of high-risk ALL protocols, directing ABL-class cases to imatinib or dasatinib and JAK-pathway cases to ruxolitinib trials.
- Efficacy of kinase inhibitors in Ph-like ALL is still being established in trials.
Similar pages
not linked directly; found by shared links- Key paperDeletion of IKZF1 and prognosis in acute lymphoblastic leukaemia
Shares Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), New England Journal of Medicine.
- Key paperAcute lymphoblastic leukaemia in children (review)
Shares Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), New England Journal of Medicine.