Abstract
With the combination of immunophenotyping and molecular tests, it is still a challenge to identify the characteristics of T cell acute lymphoblastic leukemia (T-ALL) associated with distinct outcomes. This study tests the possible correlation of cellular expression of CD135 and CD117 with somatic gene mutations in T-ALL. One hundred sixty-two samples were tested, including 143 at diagnosis, 15 from T-lymphoblastic lymphoma at relapse, and four relapse samples from sequential follow-up of T-ALL. CD135 and CD117 monoclonal antibodies were included in the T-ALL panel of flow cytometry. The percentage of cells positivity and the median fluorescence intensity were correlated with gene mutational status. STIL-TAL1, TLX3, FLT3 and IL7R mutations were tested using standard techniques. STIL-TAL1 was found in 24.8%, TLX3 in 12%, IL7R in 10% and FLT3-ITD in 5% of cases. FLT3 and IL7R mutations were mutually exclusive, as were FLT3-ITD and STIL-TAL1. Associations of CD135(high) (p<0.01), CD117(intermediate/high) (p=0.02) and FLT3-ITD, CD117(low) with IL7R(mutated) (p<0.01) and CD135(high) with TLX3(pos) were observed. We conclude that the addition of CD135 and CD117 to the diagnosis can predict molecular aberrations in T-ALL settings, mainly segregating patients with FLT3-ITD, who would benefit from treatment with inhibitors of tyrosine.
Keywords:
CD117; CD135, IL7R, TLX3; FLT3 mutations; T-cell acute lymphoblastic leukemia.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Antibodies, Monoclonal
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Antineoplastic Agents / therapeutic use
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / immunology
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / immunology
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Child
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Child, Preschool
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Female
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Gene Expression
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / immunology
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Humans
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Immunophenotyping
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Infant
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / immunology
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Male
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Mutation
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / immunology
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / immunology
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Proto-Oncogene Proteins c-kit / genetics*
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Proto-Oncogene Proteins c-kit / immunology
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Receptors, Interleukin-7 / genetics*
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Receptors, Interleukin-7 / immunology
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Recurrence
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T-Cell Acute Lymphocytic Leukemia Protein 1
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Young Adult
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fms-Like Tyrosine Kinase 3 / genetics*
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fms-Like Tyrosine Kinase 3 / immunology
Substances
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Antibodies, Monoclonal
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Antineoplastic Agents
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Basic Helix-Loop-Helix Transcription Factors
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Biomarkers, Tumor
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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Oncogene Proteins, Fusion
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Receptors, Interleukin-7
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STIL protein, human
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T-Cell Acute Lymphocytic Leukemia Protein 1
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TLX3 protein, human
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TAL1 protein, human
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FLT3 protein, human
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Proto-Oncogene Proteins c-kit
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fms-Like Tyrosine Kinase 3