{"entity":{"id":"all-ph-like","kind":"cancer","name":"Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL)","aka":["Ph-like ALL","BCR::ABL1-like ALL","B-ALL with BCR::ABL1-like features"],"tldr":"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.","summary":"Two groups reported in 2009 that a subset of B-ALL without BCR::ABL1 shared its gene-expression profile and its poor prognosis: '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.\n\nPh-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.\n\nWhether 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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemia","links":[{"label":"Wikipedia: Acute lymphoblastic leukaemia","url":"https://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemia"},{"label":"NCI PDQ: Childhood ALL Treatment","url":"https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq"}],"tags":["subtype-page","paediatric"],"related":["all-paediatric-ph-positive","all-paediatric-high-risk","aya-cancers"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","flow-cytometry-mrd"],"targets":["jak2","epor","pdgfrb","bcr-abl","cd19"],"drugs":[],"companies":[],"institutions":["childrens-oncology-group","st-jude"],"pathways":[],"terms":["philadelphia-chromosome","mrd","ph-like-all","b-all-cytogenetic-risk"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"paediatric","burden":"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.","subtypes":["Ph-like ALL with CRLF2 rearrangement (P2RY8::CRLF2 or IGH::CRLF2, often with JAK2 or JAK1 mutation)","Ph-like ALL with ABL-class fusions (ABL1, ABL2, CSF1R, PDGFRB; dasatinib- and imatinib-sensitive)","Ph-like ALL with JAK2 or EPOR rearrangements (ruxolitinib-sensitive in vitro)","Ph-like ALL with other JAK-STAT or RAS-pathway mutations (IL7R, SH2B3, FLT3, NRAS, KRAS)","Down syndrome-associated B-ALL with CRLF2 rearrangement"],"biomarkers":["Ph-like gene expression signature (low-density array or RNA sequencing)","CRLF2 overexpression by flow cytometry and CRLF2 rearrangement by FISH","ABL-class, JAK2 and EPOR fusions by FISH or RNA sequencing","JAK1, JAK2, IL7R and SH2B3 mutations","IKZF1 deletion","Flow cytometry MRD at end of induction and consolidation"],"standardOfCare":[{"setting":"Diagnosis","approach":"Screen every B-ALL without BCR::ABL1 for the Ph-like signature and identify the kinase lesion; treat as high risk with MRD monitoring.","refs":["cgp","flow-cytometry-mrd","ngs-mrd-clonoseq"],"guideline":{"version":"NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)","url":"https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq"}},{"setting":"ABL-class fusions","approach":"Dasatinib or imatinib added to high-risk chemotherapy from induction, as for Ph-positive ALL.","refs":["dasatinib","imatinib","pdgfrb"],"guideline":{"version":"NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)","url":"https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq"}},{"setting":"CRLF2, JAK2 or EPOR lesions","approach":"High-risk chemotherapy; ruxolitinib added in trials (AALL1521).","refs":["ruxolitinib","jak2","epor"],"guideline":{"version":"NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)","url":"https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq"}},{"setting":"Persistent residual disease","approach":"Blinatumomab or CD19 CAR T-cells to clear residual disease, then allogeneic transplant.","refs":["blinatumomab","tisagenlecleucel","allogeneic-hsct"],"guideline":{"version":"NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)","url":"https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq"}}],"stateOfArt":["Ph-like ALL is a WHO entity screened for at diagnosis in cooperative group trials, with the kinase lesion determining which inhibitor is tried.","ABL-class fusions are treated with dasatinib on the Ph-positive model; the benefit of ruxolitinib for JAK-pathway disease is still being tested.","CD19 immunotherapy works irrespective of the kinase lesion and is the rescue for persistent residual disease."],"history":[{"year":2009,"title":"Ph-like (BCR-ABL1-like) ALL described by Dutch and US groups as a poor-prognosis subgroup","refs":[]},{"year":2014,"title":"Sequencing shows kinase-activating lesions in nearly all Ph-like ALL, many drug-sensitive","refs":["bcr-abl","jak2"]},{"year":2016,"title":"AALL1521 opens: ruxolitinib with chemotherapy for CRLF2 and JAK-pathway Ph-like ALL","refs":["ruxolitinib"]},{"year":2022,"title":"WHO classifies B-ALL with BCR::ABL1-like features as an entity","refs":[]}],"pipeline":["ruxolitinib","dasatinib","blinatumomab","tisagenlecleucel","ngs-mrd-clonoseq","cgp"],"openProblems":["Whether kinase inhibitors improve cure rather than early response in Ph-like ALL.","Screening is unavailable in most of the world, so most Ph-like patients are never identified.","CRLF2-rearranged disease carries RAS and JAK mutations together and is less dependent on a single kinase."],"parent":"all-leukemia"},"route":"/cancers/all-ph-like/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"aya-cancers","kind":"cancer","name":"Adolescent and young adult cancers (ages 15 to 39)","route":"/cancers/aya-cancers/"},{"id":"all-paediatric-high-risk","kind":"cancer","name":"High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)","route":"/cancers/all-paediatric-high-risk/"},{"id":"all-paediatric-ph-positive","kind":"cancer","name":"Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)","route":"/cancers/all-paediatric-ph-positive/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"flow-cytometry-mrd","kind":"technology","name":"Multiparameter flow cytometry MRD","route":"/technologies/flow-cytometry-mrd/"},{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","route":"/technologies/ngs-mrd-clonoseq/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"bcr-abl","kind":"target","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/targets/bcr-abl/"},{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"},{"id":"epor","kind":"target","name":"Erythropoietin receptor (EPOR)","route":"/targets/epor/"},{"id":"jak2","kind":"target","name":"JAK2","route":"/targets/jak2/"},{"id":"pdgfrb","kind":"target","name":"PDGFRB","route":"/targets/pdgfrb/"}],"institution":[{"id":"childrens-oncology-group","kind":"institution","name":"Children's Oncology Group (COG)","route":"/institutions/childrens-oncology-group/"},{"id":"st-jude","kind":"institution","name":"St. Jude Children's Research Hospital","route":"/institutions/st-jude/"}],"term":[{"id":"b-all-cytogenetic-risk","kind":"term","name":"B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)","route":"/terms/b-all-cytogenetic-risk/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"ph-like-all","kind":"term","name":"Ph-like (BCR::ABL1-like) acute lymphoblastic leukaemia","route":"/terms/ph-like-all/"},{"id":"philadelphia-chromosome","kind":"term","name":"Philadelphia chromosome (Ph+, BCR::ABL1)","route":"/terms/philadelphia-chromosome/"}],"drug":[{"id":"blinatumomab","kind":"drug","name":"Blinatumomab","route":"/drugs/blinatumomab/"},{"id":"dasatinib","kind":"drug","name":"Dasatinib","route":"/drugs/dasatinib/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"ruxolitinib","kind":"drug","name":"Ruxolitinib","route":"/drugs/ruxolitinib/"},{"id":"tisagenlecleucel","kind":"drug","name":"Tisagenlecleucel","route":"/drugs/tisagenlecleucel/"}],"trial":[{"id":"nct07387926","kind":"trial","name":"Safety and Efficacy of Asciminib in Pediatrics and Young Adults With Relapse/Refractory (r/r) Philadelphia Positive (Ph+) or ABL-class Ph-like Acute Lymphoblastic Leukemia (ALL)","route":"/trials/nct07387926/"}]}}