title: Immunophenotyping with CD135 and CD117 predicts the FLT3, IL-7R and TLX3 gene mutations in childhood T-cell acute leukemia.
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.
authors: Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Elda Pereira
authors: EP
authors: Noronha
authors: Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Francianne Gomes
authors: FG
authors: Andrade
authors: Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Carolina
authors: C
authors: Zampier
authors: Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Camilla F C G
authors: CF
authors: de Andrade
authors: Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Eugênia
authors: E
authors: Terra-Granado
authors: Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: mpombo@inca.gov.br.
authors: Maria S
authors: MS
authors: Pombo-de-Oliveira
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000276:immunology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008297:Male; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000276:immunology; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000276:immunology; D012008:Recurrence; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D019009:Proto-Oncogene Proteins c-kit; D020395:Receptors, Interleukin-7; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D051941:fms-Like Tyrosine Kinase 3; C071236:STIL protein, human; C489494:TLX3 protein, human; C067143:TAL1 protein, human; C497970:FLT3 protein, human
keywords: CD117; CD135, IL7R, TLX3; FLT3 mutations; T-cell acute lymphoblastic leukemia