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Why and how to treat Ph-like ALL?
1Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, MS342, Memphis, TN, 38105, USA.
Best Practice & Research. Clinical Haematology
|November 24, 2018
Summary
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype. Targeted therapies, including tyrosine kinase inhibitors, show promise for treating specific genetic alterations in Ph-like ALL.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-cell precursor ALL.
- It shares a gene expression profile with Ph-positive ALL, has frequent IKZF1 alterations, and a poor prognosis.
- Ph-like ALL affects all age groups, with prevalence increasing in young adults.
Purpose of the Study:
- To review the genetic landscape of Ph-like ALL.
- To discuss targeted therapeutic strategies based on identified genetic alterations.
- To highlight the development of diagnostic screening and precision medicine trials.
Main Methods:
- Review of preclinical studies and anecdotal reports.
- Analysis of genetic alterations in Ph-like ALL.
- Examination of targeted therapy approaches.
Main Results:
- Ph-like ALL harbors diverse genetic alterations activating cytokine receptor and kinase signaling.
- Alterations fall into two main groups: ABL-class or JAK-STAT pathway activation.
- ABL-class fusions may respond to ABL1-inhibitors; JAK-STAT alterations to JAK inhibitors.
Conclusions:
- Ph-like ALL is a heterogeneous subtype requiring targeted treatment strategies.
- Precision medicine approaches, including tyrosine kinase inhibitors, are crucial for improving outcomes.
- Ongoing diagnostic screening and clinical trials aim to optimize chemotherapy combined with targeted therapies.
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