Immunophenotyping with CD135 and CD117 predicts the FLT3, IL-7R and TLX3 gene mutations in childhood T-cell acute leukemia

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 ge...

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Published in:	Blood cells, molecules, & diseases Vol. 57; pp. 74 - 80
Main Authors:	Noronha, Elda Pereira, Andrade, Francianne Gomes, Zampier, Carolina, de Andrade, Camilla F.C.G., Terra-Granado, Eugênia, Pombo-de-Oliveira, Maria S., Melaragno, Renato, Aranciba, Alejandro Mauricio, de Oliveira, Claudia Teresa, Ikoma, Maura R.V., Nóbrega, Andrea Gadelha, Fialho, Eloisa Cartaxo C., Neves, Gustavo Ribeiro, Magalhães, Isis Maria Quezado, Cordoba, José Carlos, de Brito, Patricia Caneiro, Dias, Anna Carolina Silva, Costa, Juliana Teixeira, Souza, Luciana Nunes Silva, Santos, Marcelo, Basegio, Rosania Maria
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-03-2016
Subjects:	Adolescent Antibodies, Monoclonal Antineoplastic Agents - therapeutic use Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - immunology Biomarkers, Tumor - genetics Biomarkers, Tumor - immunology CD117 CD135, IL7R, TLX3 Child Child, Preschool Female FLT3 mutations fms-Like Tyrosine Kinase 3 - genetics fms-Like Tyrosine Kinase 3 - immunology Gene Expression Homeodomain Proteins - genetics Homeodomain Proteins - immunology Humans Immunophenotyping Infant Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - immunology Male Mutation Oncogene Proteins, Fusion - genetics Oncogene Proteins, Fusion - immunology Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology Protein Kinase Inhibitors - therapeutic use Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - immunology Proto-Oncogene Proteins c-kit - genetics Proto-Oncogene Proteins c-kit - immunology Receptors, Interleukin-7 - genetics Receptors, Interleukin-7 - immunology Recurrence T-cell acute lymphoblastic leukemia T-Cell Acute Lymphocytic Leukemia Protein 1 Young Adult ALL RS TCR BFM BM mut DS T-cell acute lymphoblastic leukemia MFI FITC GBTLI-ALL WBC CD117 WT AML M-FCM SSC FLT3 mutations EGIL MoAb Bcp-ALL CD135, IL7R, TLX3 TKD T-LL RSL Neg PB APC PE Pos cy ITD PerCP T-ALL T-LL
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Summary:	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 CD135high (p<0.01), CD117intermediate/high (p=0.02) and FLT3-ITD, CD117low with IL7Rmutated (p<0.01) and CD135high with TLX3pos 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1079-9796 1096-0961
DOI:	10.1016/j.bcmd.2015.12.003