Abstract
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently identified high risk disease subtype characterized by a gene expression profile similar to that observed in Philadelphia chromosome-positive (Ph-positive) ALL, but without an underlying BCR-ABL1 translocation. Adults and children with Ph-like ALL harbor a diversity of alterations that all lead to activated kinase signaling. Outcomes for patients with Ph-like ALL are poor, which has prompted investigation into the role of tyrosine kinase inhibitor (TKI)-based therapies for this disease. Several clinical trials are now ongoing that include screening for the Ph-like signature and treatment of patients with Ph-like ALL with TKI therapy. This review examines how testing for Ph-like ALL is being incorporated into clinical trials.
Keywords:
Acute lymphoblastic leukemia; Dasatinib; Imatinib; Janus kinase inhibitor; Philadelphia chromosome-like; Ruxolitinib; tyrosine kinase inhibitor.
Copyright © 2017. Published by Elsevier Ltd.
MeSH terms
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Antineoplastic Agents / therapeutic use*
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Clinical Trials as Topic
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Dasatinib / therapeutic use
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Gene Expression Regulation, Leukemic*
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Hematopoietic Stem Cell Transplantation*
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Humans
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Imatinib Mesylate / therapeutic use
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Janus Kinases / antagonists & inhibitors
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Janus Kinases / genetics
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Janus Kinases / metabolism
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Molecular Targeted Therapy
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Nitriles
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Philadelphia Chromosome
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
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Protein Kinase Inhibitors / therapeutic use*
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Pyrazoles / therapeutic use
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Pyrimidines
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STAT Transcription Factors / antagonists & inhibitors
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STAT Transcription Factors / genetics
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STAT Transcription Factors / metabolism
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Signal Transduction
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Survival Analysis
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Transplantation, Homologous
Substances
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Antineoplastic Agents
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Nitriles
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Protein Kinase Inhibitors
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Pyrazoles
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Pyrimidines
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STAT Transcription Factors
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ruxolitinib
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Imatinib Mesylate
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Janus Kinases
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Dasatinib