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Ph-like leukaemia has the gene-expression fingerprint of Philadelphia-positive leukaemia without the Philadelphia chromosome; behind it are dozens of kinase fusions and JAK pathway lesions, and finding which one is present tells doctors whether an imatinib-type drug or a JAK inhibitor might be added to chemotherapy.
What is measured: a gene expression signature resembling BCR::ABL1-positive ALL, and then the lesion driving it. How: the signature by low-density array, RNA sequencing or a targeted classifier; the driver by flow cytometry for CRLF2 overexpression and FISH for CRLF2 rearrangement (IGH::CRLF2 or P2RY8::CRLF2, about half of cases, usually with JAK2 or JAK1 mutations), FISH or RNA sequencing for ABL-class fusions (ABL1, ABL2, PDGFRB, CSF1R), JAK2 and EPOR rearrangements, and sequencing for JAK1, JAK2, IL7R and SH2B3 mutations; IKZF1 deletion is common. It accounts for 10 to 15 percent of childhood, 25 to 30 percent of adolescent and young adult and about 20 percent of adult B-ALL, more often in people of Hispanic ancestry, with high residual disease after induction and shorter survival on chemotherapy alone. What a positive result changes: ABL-class fusions get dasatinib or imatinib added, as for Ph-positive disease; JAK-STAT lesions are treated with ruxolitinib in trials (COG AALL1521); everyone is treated on high-risk arms with residual disease measured closely, and blinatumomab, inotuzumab or CAR-T are used for persistent disease with transplant considered in first remission. Where it matters: the Ph-like ALL page, adult ALL and high-risk childhood ALL.
Shares Philadelphia chromosome (Ph+, BCR::ABL1), Dasatinib, Imatinib, Minimal / molecular residual disease (MRD).
Shares B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status), Philadelphia chromosome (Ph+, BCR::ABL1), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Dasatinib.
Shares Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Ruxolitinib, Acute lymphoblastic leukaemia.
Shares Dasatinib, Blinatumomab, Imatinib, Acute lymphoblastic leukaemia.
Shares Dasatinib, Blinatumomab, Imatinib, Acute lymphoblastic leukaemia.
Shares Blinatumomab, Imatinib, Acute lymphoblastic leukaemia.
Shares Flow cytometry (immunophenotyping), Philadelphia chromosome (Ph+, BCR::ABL1), Acute lymphoblastic leukaemia.
Shares Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL).