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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Ph-like leukaemia behaves like Philadelphia chromosome-positive leukaemia, with the same kind of overactive growth signalling, but lacks the BCR::ABL1 gene itself. It is caused by a scattered set of gene fusions and mutations, many of them blockable by existing kinase pills such as dasatinib or ruxolitinib, and it is now screened for at diagnosis so those drugs can be tried.
Two groups reported in 2009 that a subset of B-ALL without BCR::ABL1 shared its gene-expression profile and its high risk of relapse: 'BCR-ABL1-like' from the Dutch Childhood Oncology Group and 'Ph-like' from St Jude and the Children's Oncology Group. Whole-genome and transcriptome sequencing, reported in the New England Journal of Medicine in 2014, showed that nearly all of these leukaemias carried a kinase-activating lesion: rearrangements of CRLF2 in about half, with JAK1 or JAK2 mutations in roughly half of those; ABL-class fusions of ABL1, ABL2, CSF1R or PDGFRB in about one in eight; JAK2 or EPOR rearrangements; and mutations in IL7R, SH2B3, FLT3 and the RAS pathway. IKZF1 deletions accompany most. In cell lines and patient samples, ABL-class fusions responded to imatinib and dasatinib and JAK-STAT lesions to ruxolitinib.
Ph-like ALL is now a WHO 2022 entity, B-ALL with BCR::ABL1-like features, and cooperative groups screen for it at diagnosis by a low-density gene expression array or RNA sequencing followed by FISH or PCR for the specific lesion. Its outcome on chemotherapy is poor because induction leaves high residual disease, so most patients are treated as high risk with intensified therapy and, when residual disease persists, allogeneic transplant. The Children's Oncology Group added dasatinib to chemotherapy for ABL-class fusions in AALL1131 and tested ruxolitinib with chemotherapy for CRLF2 and JAK-pathway disease in AALL1521, and the same lesions are treated with kinase inhibitors in adults on trial. Because the CD19 antigen is unaffected, blinatumomab and CD19 CAR T-cells work as in other B-ALL and are the standard rescue when residual disease does not clear.
| Setting | Approach | Guideline |
|---|---|---|
| Diagnosis | Screen every B-ALL without BCR::ABL1 for the Ph-like signature and identify the kinase lesion; treat as high risk with MRD monitoring. | not mapped |
| ABL-class fusions | Dasatinib or imatinib added to high-risk chemotherapy from induction, as for Ph-positive ALL. | not mapped |
| CRLF2, JAK2 or EPOR lesions | High-risk chemotherapy; ruxolitinib added in trials (AALL1521). | not mapped |
| Persistent residual disease | Blinatumomab or CD19 CAR T-cells to clear residual disease, then allogeneic transplant. | not mapped |