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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.
Whether a kinase inhibitor added to chemotherapy improves cure, rather than just early response, is not settled: the Ph-positive experience with imatinib is the model, but Ph-like disease is heterogeneous, and CRLF2-rearranged leukaemia, which also carries JAK and RAS mutations, is less kinase-dependent than ABL-class disease. Screening is still uneven outside trial centres and in lower-income countries, so many patients are never identified. Down syndrome-associated ALL, CRLF2-rearranged in over half of cases, sits at the boundary and has its own toxicity constraints. Ph-like ALL is also over-represented among Hispanic and Latino children, linked to inherited GATA3 variants, one of the clearest examples of an inherited contribution to a childhood cancer subtype.
About one in ten children with standard-risk B-cell ALL, one in seven with high-risk disease and around a quarter of adolescents and young adults with B-ALL have a Ph-like signature, making it one of the commonest high-risk subtypes.
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
Screen every B-ALL without BCR::ABL1 for the Ph-like signature and identify the kinase lesion; treat as high risk with MRD monitoring.
Dasatinib or imatinib added to high-risk chemotherapy from induction, as for Ph-positive ALL.
High-risk chemotherapy; ruxolitinib added in trials (AALL1521).
Blinatumomab or CD19 CAR T-cells to clear residual disease, then allogeneic transplant.
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The structure of the paediatric ALL subtype pages, from risk groups to new targeted and immune therapies, follows the framework in this review.
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.
This discovery, made simultaneously with the American Children's Oncology Group finding, created the Ph-like ALL category now screened for in high-risk protocols.
IKZF1 status is part of risk stratification in several paediatric ALL protocols and is a hallmark of Ph-like ALL.
Query for this cancer: (TITLE:"Philadelphia chromosome-like acute lymphoblastic leukaemia" OR ABSTRACT:"Philadelphia chromosome-like acute lymphoblastic leukaemia" OR TITLE:"Ph-like or BCR::ABL1-like ALL" OR ABSTRACT:"Ph-like or BCR::ABL1-like ALL" OR TITLE:"Ph-like ALL" OR ABSTRACT:"Ph-like ALL" OR TITLE:"BCR::ABL1-like ALL" OR ABSTRACT:"BCR::ABL1-like ALL" OR TITLE:"B-ALL with BCR::ABL1-like features" OR ABSTRACT:"B-ALL with BCR::ABL1-like features") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), not a curated reading list.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Fever of 38 C or higher, chills, low blood pressure, fast heartbeat or breathlessness, especially after a step-up dose. Boxed warning on teclistamab, epcoritamab, glofitamab, tarlatamab and blinatumomab.
Fever of 38 C or higher is grade 1 CRS; fever with low blood pressure, fast heartbeat, breathlessness or low oxygen is grade 2 or higher. The labels carry a boxed warning and say to report fever immediately.
Take with a meal and a large glass of water.
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
Reduce dose for CrCl below 60 with platelets under 150; dialysis dosing after each session.
See all on the product pages:BlinatumomabDasatinibImatinibRuxolitinibTisagenlecleucel·Printable cards in the navigator
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