# Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL)

Source: https://onco.cc/cancers/all-ph-like/  
OnCo record `all-ph-like` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Ph-like ALL; BCR::ABL1-like ALL; B-ALL with BCR::ABL1-like features
- Tags: subtype-page; paediatric
- 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/all-ph-like/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/all-ph-like/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/all-ph-like/#what-it-is [5 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/all-ph-like/#finding-it [6 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/all-ph-like/#treating-it [4 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/all-ph-like/#evidence [3 trials, 4 key papers, 4 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/all-ph-like/#science [10 targets]
- Countries and centres (own page): 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. https://onco.cc/cancers/all-ph-like/where-you-are/ [1 centre]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/all-ph-like/#living-with-it [17 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/all-ph-like/coming/ [5 medicines, 3 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/all-ph-like/data/ [40 connected records]

## Standard of care

- 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. ([Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/))
- ABL-class fusions: Dasatinib or imatinib added to high-risk chemotherapy from induction, as for Ph-positive ALL. ([Dasatinib](https://onco.cc/drugs/dasatinib/), [Imatinib](https://onco.cc/drugs/imatinib/), [PDGFRB](https://onco.cc/targets/pdgfrb/))
- CRLF2, JAK2 or EPOR lesions: High-risk chemotherapy; ruxolitinib added in trials (AALL1521). ([Ruxolitinib](https://onco.cc/drugs/ruxolitinib/), [JAK2](https://onco.cc/targets/jak2/), [Erythropoietin receptor (EPOR)](https://onco.cc/targets/epor/), [AALL1521](https://onco.cc/trials/aall1521/))
- Persistent residual disease: Blinatumomab or CD19 CAR T-cells to clear residual disease, then allogeneic transplant. ([Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemia
- Wikipedia: Acute lymphoblastic leukaemia: https://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemia
- NCI PDQ: Childhood ALL Treatment: https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq

## Connected records

- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Adolescent and young adult cancers (ages 15 to 39)](https://onco.cc/cancers/aya-cancers/), [High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)](https://onco.cc/cancers/all-paediatric-high-risk/), [Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year)](https://onco.cc/cancers/all-infant/), [Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)](https://onco.cc/cancers/all-paediatric-ph-positive/), [Relapsed and refractory acute lymphoblastic leukaemia in children](https://onco.cc/cancers/all-paediatric-relapsed/), [Standard-risk B-cell acute lymphoblastic leukaemia in children](https://onco.cc/cancers/all-paediatric-standard-risk/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/targets/bcr-abl/), [CD19](https://onco.cc/targets/cd19/), [Erythropoietin receptor (EPOR)](https://onco.cc/targets/epor/), [JAK2](https://onco.cc/targets/jak2/), [PDGFRB](https://onco.cc/targets/pdgfrb/)
- companies: [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/)
- institutions: [St. Jude Children's Research Hospital](https://onco.cc/institutions/st-jude/)
- terms: [B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)](https://onco.cc/terms/b-all-cytogenetic-risk/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Ph-like (BCR::ABL1-like) acute lymphoblastic leukaemia](https://onco.cc/terms/ph-like-all/), [Philadelphia chromosome (Ph+, BCR::ABL1)](https://onco.cc/terms/philadelphia-chromosome/)
- key papers: [A subtype of childhood acute lymphoblastic leukaemia with poor outcome: genome-wide classification study (BCR-ABL1-like ALL)](https://onco.cc/key-papers/paper-den-boer-bcr-abl1-like-all-lancet-oncol-2009/), [Acute lymphoblastic leukaemia in children (review)](https://onco.cc/key-papers/paper-hunger-mullighan-all-children-nejm-2015/), [Deletion of IKZF1 and prognosis in acute lymphoblastic leukaemia](https://onco.cc/key-papers/paper-mullighan-ikzf1-nejm-2009/), [Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukaemia](https://onco.cc/key-papers/paper-roberts-ph-like-all-nejm-2014/)
- drugs: [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Imatinib](https://onco.cc/drugs/imatinib/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/), [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/)
- trials: [AALL1521](https://onco.cc/trials/aall1521/), [Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations](https://onco.cc/trials/nct02883049/), [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)](https://onco.cc/trials/nct07387926/)

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JSON: https://onco.cc/api/v1/entities/all-ph-like.json