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

Noronha, Elda Pereira; Fg, Andrade; Zampier, Carolina Da Paz; Cf, de Andrade; Terra-Granado, Eugênia; Pombo‐de‐Oliveira, Maria S.

doi:10.1016/j.bcmd.2015.12.003

Cited by 11 publications

(13 citation statements)

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“…In all cases, the immunophenotyping by multiparametric flow cytometry was performed utilizing the panel of monoclonal antibodies in Supplementary Table 1. FACS Calibur and FACS Canto II flow cytometers (Becton, Dickinson, and Company, CA, USA) were used for the sample acquisition and all the immunophenotypic analyses were performed in the Infinicyt™ program version 1.8 (Cytognos—Salamanca—Spain), according to previously published procedures (16, 17). A sample was considered positive for a marker when at least 20% of lymphoblasts in a CD45 low / intermediate gate had its expression.…”

Section: Methodsmentioning

confidence: 99%

The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia

et al. 2019

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T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous malignancy, which reflects distinctive stages of T-cell differentiation arrest. We have revisited a cohort of pediatric T-ALL, in order to test if immunophenotypes associated with molecular alterations would predict the patient's outcome. Genetic mutations, translocations and copy number alterations were identified through Sanger sequencing, RT-PCR, FISH and multiplex ligation-dependent probe amplification (MLPA). We defined 8 immunophenotypic T-ALL subtypes through multiparametric flow cytometry: early T-cell precursor (ETP, n = 27), immature ( n = 38), early cortical ( n = 15), cortical ( n = 50), late cortical ( n = 53), CD4/CD8 double negative mature ( n = 31), double positive mature ( n = 35) and simple positive mature ( n = 31) T-ALL. Deletions (del) or amplifications (amp) in at least one gene were observed in 87% of cases. The most frequent gene alterations were CDKN2A/B del (71.4%), NOTCH1 mut (47.6%) and FBXW7 mut (17%). ETP-ALL had frequent FLT3 mut (22.2%) and SUZ12 del (16.7%) ( p < 0.001), while CDKN2A/B del were rarely found in this subtype ( p < 0.001). The early cortical T-ALL subtype had high frequencies of NOTCH1 mut and IL7R mut (71%, 28.6%, respectively), whereas, mature T-ALL with double positive CD4/CD8 had the highest frequencies of STIL-TAL1 (36.7%), LEF1 del (27.3%) and CASP8AP2 del (22.7%). The co-existence of two groups of T-ALL with NOTCH1 mut /IL7R mut , and with TLX3/SUZ12 del /NF1 del / IL7R mut , were characterized with statistical significance ( p < 0.05) but only STIL-TAL1 (pOS 47.5%) and NOTCH1 WT / FBXW7 WT (pOS 55.3%) are predictors of poor T-ALL outcomes. In conclusion, we have observed that 8 T-ALL subgroups are characterized by distinct molecular profiles. The mutations in NOTCH1/FBXW7 and STIL-TAL1 rearrangement had a prognostic impact, independent of immunophenotype.

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Section: Methodsmentioning

confidence: 99%

The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia

et al. 2019

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“…Bone marrow (BM) aspirates and/or peripheral blood (PB) samples were sent to the Pediatric Hematology-Oncology Research Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. Morphology, immunophenotyping by multiparametric flow cytometry (M-FCM), and molecular tests were performed as previously described ( 12 – 14 ). The diagnosis of acute leukemia subtypes followed the World Health Organization (WHO) criteria ( 15 ).…”

Section: Methodsmentioning

confidence: 99%

CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia

Lvc

Noronha

et al. 2018

Front. Oncol.

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CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in N/KRAS, NOTCH1, FBXW7 as well as STIL-TAL1 and TLX3 rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1–1272), T-ALL was relatively low, with MFI 43.2 (1.9–1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1aneg) had a lower CD44 expression, MFI 57.5 (2.7–866.3), whereas mCD3/TCRγδpos cases had higher expressions, MFI 99.9 (16.4–866.3). NOTCH1mut and STIL-TAL1 were associated with low CD44 expression, whereas N/KRASmut and FBXW7mut cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (p = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL.

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“…(Sharma et al, 2016) A adição dos marcadores CD135 e CD117 ao diagnóstico pode prever aberrações moleculares em configurações de T-ALL em crianças, principalmente segregando pacientes com FLT3-ITD, que se beneficiariam do tratamento com inibidores de tirosina. (Noronha et al, 2016) Para Ren et al (2019) a combinação dos anticorpos CD9, CD11b e HLA-DR apresenta alta sensibilidade e especificidade e pode ser utilizada para diagnosticar APL. Já no diagnóstico de MPAL são avaliados os anticorpos TdT, CD2, CD5 e CD7.…”

Section: Discussõesunclassified

Análise de métodos imunofenotípicos no diagnóstico precoce de leucemias agudas

Santos¹,

Leite²,

Abreu³

et al. 2020

RSD

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Objetivo: Evidenciar a importância da utilização da imunofenotipagem no diagnóstico precoce de leucemias agudas. Metodologia: Trata-se de uma revisão integrativa da literatura, onde foram utilizados 12 artigos publicados entre 2016 e 2020. O idioma dos artigos referenciados foram inglês e francês, coletados no Scielo, LILACS, BVS e EBSCO. Utilizando a busca avançada para os seguintes descritores: Immunophenotyping, Acute Leukemia, Flow cytometry. Resultado: Os artigos utilizados foram publicados entre os anos de 2016 e 2020. Os artigos explicitaram que o uso da imunofenotipagem, especificamente a citometria de fluxo, é um método de extrema importância para o diagnóstico de leucemias agudas. Foram apontados marcadores utilizados em cada tipo e subtipo de leucemia, evidenciando assim a peculiaridade da doença. Conclusão: A utilização de métodos imunofenotípicos com exames de rotina contribui no diagnóstico precoce de pacientes com leucemias agudas, fazendo com que o tratamento seja feito também de forma precoce, aumentando assim a sobrevida desses indivíduos. De acordo com os estudos analisados, a imunofenotipagem está em constante evolução e promete simplificar o processo de diagnóstico de vários tipos de leucemias.

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

Cited by 11 publications

References 30 publications

The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia

The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia

CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia

Análise de métodos imunofenotípicos no diagnóstico precoce de leucemias agudas

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