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1.
Leuk Lymphoma ; 61(14): 3460-3467, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32779947

RESUMO

To evaluate the optimal time to monitor minimal residual disease (MRD) for pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL). Children newly diagnosed with T-ALL were treated per the CCLG-ALL2008 protocol in our hospital. MRD was monitored at days 15, 33 and 90, and the patients were stratified as low-, intermediate- or high-risk according to MRD at days 33 and 90. The 5-year event-free survival (EFS) and overall survival (OS) rates for all patients were 60.1 ± 5.6% and 63.1 ± 5.6%, respectively. The median follow-up time was 54 (0.3-120) months. Univariate analysis showed that the 5-year EFS rate correlated with MRD at days 33 and 90 (p < .01). Multivariate analysis demonstrated that only MRD at day 90 and involvement of the central nervous system (CNS) were independent prognostic factors. MRD at day 90 likely provides better prognostic value for pediatric T-ALL patients. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00707083.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Intervalo Livre de Doença , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Linfócitos T
2.
Cancer Med ; 9(18): 6825-6835, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32706183

RESUMO

BACKGROUND: Obesity is a risk factor for many adulthood cancers, but its role in childhood, adolescent, and young adult (AYA) cancer is unknown. Childhood and AYA acute lymphoblastic leukemia (ALL) incidence and obesity prevalence have shown concurrent increases. We sought to identify whether obesity may be a risk factor for childhood and AYA ALL. METHODS: Characteristics from individuals with ALL, aged 2-30 years, diagnosed 2004-2017 and treated on Children's Oncology Group (COG) protocols with available pre-treatment anthropometric data (N = 4726) were compared to National Health and Nutrition Examination Survey controls (COG AALL17D2). Body mass index (BMI) was defined using standard CDC definitions. Multivariate conditional logistic regression assessed associations between BMI and ALL with additional analyses stratified by sex and race/ethnicity. RESULTS: Among cases (72% high-risk (HR) B-ALL, 28% T-ALL), 5% had underweight, 58% normal weight, 17% overweight, and 20% obesity. Underweight (OR 2.11, 95% CI 1.56-2.85) and obesity (OR 1.32, 95% CI 1.15-1.53) were associated with B-ALL diagnosis. Specifically, obesity was associated with B-ALL among males (OR 1.57, 95% CI 1.30-1.91) and Hispanic children (OR 1.78, 95% CI 1.39-2.29). Obesity was also associated with central nervous system (CNS) involvement. CONCLUSION: Pre-treatment obesity is associated with HR B-ALL among males and Hispanics, as well as with CNS involvement, suggesting common physiology between obesity and leukemogenesis. An association between underweight and ALL was confirmed, likely due to cancer-associated wasting. These results have important public health implications for obesity prevention and treatment in children and adolescents to reduce cancer risk.


Assuntos
Índice de Massa Corporal , Obesidade Infantil/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Magreza/epidemiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Obesidade Infantil/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Medição de Risco , Fatores de Risco , Magreza/diagnóstico , Estados Unidos/epidemiologia , Adulto Jovem
3.
Pediatr Blood Cancer ; 66(1): e27496, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30280491

RESUMO

BACKGROUND: The leukemogenesis of T-cell acute lymphoblastic leukemia (T-ALL) involves multistep processes of genetic alterations. We aimed to determine the genetic alterations including common fusion transcripts, overexpression of T-cell transcription factor oncogenes, and deletion or mutation of targeted genes in pediatric T-ALL in Taiwan as well as their impact on outcomes in those treated with the Taiwan Pediatric Oncology Group-ALL-2002 protocol. PROCEDURE: Between 1995 and 2015, bone marrow samples obtained from 102 children aged <18 years consecutively diagnosed with T-ALL were examined. Thirty-two genetic alterations were examined by reverse transcription polymerase chain reaction (PCR) assays-PCR-based assays-followed by direct sequencing, real time quantitative PCR with TaqMan assays, or multiplex ligase probe amplification. RESULTS: TAL1 overexpression, CDKN2A/2B deletions, and NOTCH1 mutation were the most frequent aberrations while none had NF1, SUZ12 deletion, JAK1 or JAK2 mutations, or NUP214-ABL1 fusion in our cohort. The most frequent cooperating occurrence of genetic alterations included CDKN2A/2B and MTAP, MTAP and CDKN2B, LEF1 and PTPN2, and HOX11L2 and PHF6 mutation/deletion. NOTCH1 mutations conferred a favorable overall survival, whereas SIL-TAL1 fusion, TAL overexpression, LEF1 deletion, and PHF6 deletion/mutation were associated with an inferior outcome. By multivariate analysis, PHF6 mutation/deletion was the only independent predictor for inferior overall survival. CONCLUSIONS: The present study showed that the frequencies of genetic alterations in Taiwanese children with T-ALL differed considerably from those reported in Western countries. PHF6 mutation/deletion was an independently adverse predictor.


Assuntos
Biomarcadores Tumorais/genética , Mutação , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico , Taxa de Sobrevida , Taiwan/epidemiologia
4.
Leuk Lymphoma ; 60(5): 1171-1178, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30407885

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is a curable malignancy in the pediatric population. However, population-level data on its incidence and outcomes among adults is sparse. Using SEER database, we identified 1141 patients aged ≥20 years with pathologically confirmed T-ALL diagnosed between the years 2001 and 2014 and actively followed. Incidence of T-ALL was 0.13 cases/100,000 population with significant variations by age, gender, race, and period. The 5-year overall survival (OS) declined significantly with increasing age (age <40, 51.9%; age 40-59, 37.3%; age 60-79, 19.2%; age ≥80, 0%; p < .001) and varied by race (whites - 45.7%, blacks - 25.1%, others - 40.3%; p < .001). Over time, OS has improved significantly in patients <60 years (2001-2007, 42.8% vs 2008-2014, 53.1%; p = .005), but not in patients older than 60 years (2001-2007, 18% vs 2008-2014, 22.8%; p = .71), highlighting the need for effective and safe treatments in this population.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Gerenciamento Clínico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Vigilância em Saúde Pública , Programa de SEER , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
5.
Br J Cancer ; 118(7): 985-994, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29515258

RESUMO

BACKGROUND: Despite chemotherapy intensification, a subgroup of high-risk paediatric T-cell acute lymphoblastic leukemia (T-ALL) patients still experience treatment failure. In this context, we hypothesised that therapy resistance in T-ALL might involve aldo-keto reductase 1C (AKR1C) enzymes as previously reported for solid tumors. METHODS: Expression of NRF2-AKR1C signaling components has been analysed in paediatric T-ALL samples endowed with different treatment outcomes as well as in patient-derived xenografts of T-ALL. The effects of AKR1C enzyme modulation has been investigated in T-ALL cell lines and primary cultures by combining AKR1C inhibition, overexpression, and gene silencing approaches. RESULTS: We show that T-ALL cells overexpress AKR1C1-3 enzymes in therapy-resistant patients. We report that AKR1C1-3 enzymes play a role in the response to vincristine (VCR) treatment, also ex vivo in patient-derived xenografts. Moreover, we demonstrate that the modulation of AKR1C1-3 levels is sufficient to sensitise T-ALL cells to VCR. Finally, we show that T-ALL chemotherapeutics induce overactivation of AKR1C enzymes independent of therapy resistance, thus establishing a potential resistance loop during T-ALL combination treatment. CONCLUSIONS: Here, we demonstrate that expression and activity of AKR1C enzymes correlate with response to chemotherapeutics in T-ALL, posing AKR1C1-3 as potential targets for combination treatments during T-ALL therapy.


Assuntos
Aldo-Ceto Redutases/fisiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , 20-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , 20-Hidroxiesteroide Desidrogenases/fisiologia , Idade de Início , Membro C3 da Família 1 de alfa-Ceto Redutase/antagonistas & inibidores , Membro C3 da Família 1 de alfa-Ceto Redutase/fisiologia , Aldo-Ceto Redutases/antagonistas & inibidores , Animais , Criança , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Hidroxiesteroide Desidrogenases/fisiologia , Isoenzimas/fisiologia , Acetato de Medroxiprogesterona/administração & dosagem , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Oxirredutases/antagonistas & inibidores , Oxirredutases/fisiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Células Tumorais Cultivadas , Vincristina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
6.
J Pediatr Hematol Oncol ; 40(1): e1-e8, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29200162

RESUMO

NOTCH1/FBXW7 mutations trigger oncogenic NOTCH1 signaling and its downstream target genes play crucial roles in the molecular pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). In the present study, NOTCH1 and FBXW7 mutations were studied in 25 primary T-ALL samples. All 34 exons of NOTCH1 and hotspot exons (exon 9 and exon 10) of FBXW7 were polymerase chain reaction amplified and sequenced for mutations. Our results showed that 13/25 (52%) were NOTCH1-mutated, of which 11 patients (44%) showed mutation in the hotspot exons. Four patients (16%) had mutations in non-hotspot exons of NOTCH1. Notably, 2 T-ALL patients (8%) harbored mutations in both hotspot and non-hotspot exons of NOTCH1, whereas 2 patients (8%) had mutations in the hotspot exons of FBXW7. In all, 7 mutations were identified which were not previously reported. The real-time polymerase chain reaction study in 15 patients revealed that increased expression of activated NOTCH1 was found in NOTCH1/FBXW7 hotspot exon-mutated cases. In addition, NOTCH1/FBXW7-mutated patients had showed upregulated HES1, c-MYC, NOTCH3 gene expression. When survival analysis was performed including samples (n=50) from our previous study, an early treatment response and better survival was observed in NOTCH1/FBXW7 hotspot-mutated patients. Our study suggests that NOTCH1/FBXW7 hotspot-mutated T-ALL cases had better response to ALL BFM-95 protocol.


Assuntos
Proteína 7 com Repetições F-Box-WD/genética , Mutação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Prognóstico , Receptor Notch1/genética , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Asparaginase , Criança , Pré-Escolar , Ciclofosfamida , Citarabina , Análise Mutacional de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Mercaptopurina , Metotrexato , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Prednisona , Análise de Sobrevida , Vincristina , Adulto Jovem
7.
Eur J Med Genet ; 59(12): 641-646, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27238889

RESUMO

Early onset ataxia telangiectasia (A-T) is a neurodegenerative DNA-instability disorder, which presents early in childhood. Hallmarks of A-T are progressive ataxia and a dramatic increased risk of developing malignancies (25%), especially of hematological origin. In children these malignancies mainly concern aggressive Non-Hodgkin lymphoma, acute leukemias and Hodgkin lymphoma. Of the acute leukemias, T-cell lymphoblastic leukemia (T-ALL) is by far the most common. Since patients with A-T experience increased toxicity to radio- and chemotherapeutic treatment, the optimal treatment strategy of acute leukemia remains subject of debate. Review of literature of treatment of T-ALL in patients with A-T (n = 18) showed that many patients are not diagnosed with A-T at time of presentation of T-ALL. This implicates that physicians must be aware of symptoms of A-T in young patients presenting with T-ALL. Complete remission rates are high following upfront modified as well as unmodified treatment strategies. Treatment of ALL in children with A-T is feasible and should be performed. Definitive treatment strategy must be determined by shared decision making with patient, caretakers and medical team. Future prospective studies are needed to elucidate optimal treatment strategy.


Assuntos
Ataxia Telangiectasia/tratamento farmacológico , Ataxia Telangiectasia/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Ataxia Telangiectasia/complicações , Ataxia Telangiectasia/patologia , Criança , Intervalo Livre de Doença , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Estudos Prospectivos
8.
Leuk Lymphoma ; 57(6): 1436-41, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26380954

RESUMO

A polymorphism rs4938723 (T > C) within the promoter region of pri-miR-34b/c has been found to not only affect the expression of mature miR-34b/c but also contribute to the susceptibility to several cancer types. We designed a case-control study to evaluate the role of rs4938723 in childhood acute lymphoblastic leukemia (ALL). The rs4938723 CC genotype was significantly associated with reduced ALL risk (p = 0.003, ORadjusted = 0.51, 95% CI = 0.33-0.80 for CC vs. TT). Stratification analyses showed the differences were pronounced in older (> 6 years), male subjects, as well as in patients in low risk and T-ALL subtypes. The in vitro luciferase assays in Jurkat and K-562 cell lines showed that the transcription activity of miR-34b/c was increased when T allele transited to C allele (p < 0.05). In conclusion, rs4938723 genetic variant contributed to the susceptibility to Chinese childhood ALL by influencing the transcription activity of miR-34b/c promoter.


Assuntos
Alelos , Povo Asiático/genética , Estudos de Associação Genética , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Meio Ambiente , Feminino , Expressão Gênica , Frequência do Gene , Genótipo , Humanos , Masculino , Razão de Chances , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Regiões Promotoras Genéticas , Risco
9.
Br J Haematol ; 171(4): 574-84, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26205622

RESUMO

Infant T-cell acute lymphoblastic leukaemia (iT-ALL) is a very rare and poorly defined entity with a poor prognosis. We assembled a unique series of 13 infants with T-ALL, which allowed us to identify genotypic abnormalities and to investigate prenatal origins. Matched samples (diagnosis/remission) were analysed by single nucleotide polymorphism-array to identify genomic losses and gains. In three cases, we identified a recurrent somatic deletion on chromosome 3. These losses result in the complete deletion of MLF1 and have not previously been described in T-ALL. We observed two cases with an 11p13 deletion (LMO2-related), one of which also harboured a deletion of RB1. Another case presented a large 11q14·1-11q23·2 deletion that included ATM and only five patients (38%) showed deletions of CDKN2A/B. Four cases showed NOTCH1 mutations; in one case FBXW7 was the sole mutation and three cases showed alterations in PTEN. KMT2A rearrangements (KMT2A-r) were detected in three out of 13 cases. For three patients, mutations and copy number alterations (including deletion of PTEN) could be backtracked to birth using neonatal blood spot DNA, demonstrating an in utero origin. Overall, our data indicates that iT-ALL has a diverse but distinctive profile of genotypic abnormalities when compared to T-ALL in older children and adults.


Assuntos
Genótipo , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Idade de Início , Aneuploidia , Sequência de Bases , Proteínas de Ciclo Celular , Cromossomos Humanos Par 11/ultraestrutura , Cromossomos Humanos Par 3/ultraestrutura , Metilação de DNA , DNA de Neoplasias/genética , Proteínas de Ligação a DNA , Feminino , Doenças Fetais/genética , Deleção de Genes , Dosagem de Genes , Genes Neoplásicos , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Dados de Sequência Molecular , Mutação , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células T Precursoras/embriologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Regiões Promotoras Genéticas/genética , Proteínas/genética , Deleção de Sequência
10.
J Pak Med Assoc ; 64(5): 596-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25272555

RESUMO

Cytogenetic abnormalities have long been recognized as the genetic basis of the occurrence of various malignancies. Specific cytogenetic abnormalities have shown to occur recurrently in particular subtypes of leukaemias and lymphomas. t(1;14) is an infrequently occurring recurrent chromosomal translocation that has been described in literature to be associated with haematological malignancies. Trisomy 4 is another rare genetic abnormality which has been reported in association with both acute myeloid and lymphoid leukaemias. The concomitant occurrence of a myeloid malignancy in association with a lymphoproliferative disorder is a distinctly unusual phenomenon. We report the case of a young patient with concomitant T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia with a novel cytogenetic abnormality i.e. t(1;14) with trisomy 4. We believe this is the first reported case where a patient with two concomitant haematological malignancies, harboured this karyotype.


Assuntos
Cromossomos Humanos Par 4/genética , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Neoplasias Primárias Múltiplas , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Translocação Genética , Trissomia , Adulto , Medula Óssea/patologia , Evolução Fatal , Feminino , Humanos , Cariótipo
11.
Ann Hematol ; 92(5): 635-44, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23354995

RESUMO

Genetic alterations implicated in the leukemogenesis of T cell acute lymphoblastic leukemia (T-ALL) have been identified in recent years. In this study, we investigated gene mutation profiles and prognostic implications in a series of Korean T-ALL patients. The study patients were 29 Korean patients with T-ALL; 13 adults (45 %) and 16 children (55 %; male-to-female ratio, 25:4). Clinical, hematologic, and cytogenetic findings were reviewed. We performed mutation analyses for NOTCH1, FBXW7, PHF6, and IL7R genes and survival analyses according to the mutational status. Gene mutations were identified in 66 % of the patients in our series (19/29). Eighteen patients (62 %) had NOTCH1/FBXW7 mutations. Sixteen patients (55 %) had NOTCH1 mutations including nine novel mutations, and eight patients (28 %) had known FBXW7 mutations. Eight patients (28 %; six males and two females) had PHF6 mutations including four novel mutations. Three patients (10 %) had IL7R mutations, which were all novel in-frame insertion or deletion-insertions. The gene mutation profile combined with cytogenetics and FISH study for the p16 gene detected genetic aberrations in 90 % of patients (26/29). There was no significant difference in the frequency of gene mutations between the pediatric and adult patients with T-ALL. Survival analyses suggested a favorable prognostic implication of NOTCH1 mutations in adult T-ALL. Gene mutation studies for NOTCH1, FBXW7, PHF6, and IL7R could detect genetic alterations in a majority of Korean T-ALL patients with novel mutations. We observed similar mutation profiles between adult and pediatric T-ALL, and a favorable prognostic implication of NOTCH1 mutations in adult T-ALL.


Assuntos
Povo Asiático/genética , Análise Mutacional de DNA , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Adulto , Povo Asiático/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/etnologia , Prognóstico , República da Coreia/epidemiologia , Adulto Jovem
12.
Br J Haematol ; 156(3): 358-65, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22128890

RESUMO

Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Children's Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P=0·014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Adolescente , Antígenos CD/análise , Antígenos de Neoplasias/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunofenotipagem , Lactente , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/classificação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/cirurgia , Prednisona/administração & dosagem , Indução de Remissão , Transplante de Células-Tronco , Transplante Homólogo , Resultado do Tratamento
13.
Haematologica ; 96(12): 1808-14, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21880637

RESUMO

BACKGROUND: Mutations in the PHF6 gene were recently described in patients with T-cell acute lymphoblastic leukemia and in those with acute myeloid leukemia. The present study was designed to determine the prevalence of PHF6 gene alterations in T-cell acute lymphoblastic leukemia. DESIGN AND METHODS: We analyzed the incidence and prognostic value of PHF6 mutations in 96 Chinese patients with T-cell acute lymphoblastic leukemia. PHF6 deletions were screened by real-time quantitative polymerase chain reaction and array-based comparative genomic hybridization. Patients were also investigated for NOTCH1, FBXW7, WT1, and JAK1 mutations together with CALM-AF10, SET-NUP214, and SIL-TAL1 gene rearrangements. RESULTS: PHF6 mutations were identified in 11/59 (18.6%) adult and 2/37 (5.4%) pediatric cases of T-cell acute lymphoblastic leukemia, these incidences being significantly lower than those recently reported. Although PHF6 is X-linked and mutations have been reported to occur almost exclusively in male patients, we found no sex difference in the incidences of PHF6 mutations in Chinese patients with T-cell acute lymphoblastic leukemia. PHF6 deletions were detected in 2/79 (2.5%) patients analyzed. NOTCH1 mutations, FBXW7 mutations, WT1 mutations, JAK1 mutations, SIL-TAL1 fusions, SET-NUP214 fusions and CALM-AF10 fusions were present in 44/96 (45.8%), 9/96 (9.4%), 4/96 (4.1%), 3/49 (6.1%), 9/48 (18.8%), 3/48 (6.3%) and 0/48 (0%) of patients, respectively. The molecular genetic markers most frequently associated with PHF6 mutations were NOTCH1 mutations (P=0.003), SET-NUP214 rearrangements (P=0.002), and JAK1 mutations (P=0.005). No differences in disease-free survival and overall survival between T-cell acute lymphoblastic leukemia patients with and without PHF6 mutations were observed in a short-term follow-up. CONCLUSIONS: Overall, these results indicate that, in T-cell acute lymphoblastic leukemia, PHF6 mutations are a recurrent genetic abnormality associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214.


Assuntos
Proteínas de Transporte/genética , Chaperonas de Histonas/genética , Janus Quinase 1/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptor Notch1/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Idoso , Povo Asiático , Criança , China/epidemiologia , Proteínas de Ligação a DNA , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prevalência , Proteínas Repressoras , Fatores Sexuais
14.
Indian J Cancer ; 48(3): 310-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21921330

RESUMO

BACKGROUND: Pediatric acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease and socioeconomic and environmental factors are considered to be an important determinant of its immunophenotype. The aim of this analysis is to study the time trend in the immunophenotype of pediatric acute lymphoblastic leukemia (ALL) cases in our geographic setting. MATERIALS AND METHODS: A total of 639 new pediatric ALL cases immunophenotyped during 1989-2009 forms the basis of this analysis. Representative bone marrow or peripheral blood of these patients was immunophenotyped flowcytometrically using an extensive panel of monoclonal antibodies. RESULTS: During early phase of our study we noticed a relative excess of T-ALL and a paucity of common acute lymphoblastic leukemia (C-ALL) in contrast to western data. Over a period of 20 years we witnessed a gradual reduction in pediatric T-ALL cases and a proportionate increase in C-ALL cases. CONCLUSION: We find that this change of pattern is synchronizing with the socioeconomic and industrial development prevailing in our geographic setting and suggest a possible link between the predominant immunophenotype of pediatric ALL cases and the environmental and socioeconomic factors prevailing in that locality.


Assuntos
Anticorpos Monoclonais , Neprilisina/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem/métodos , Incidência , Índia/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia
15.
Blood ; 118(5): 1323-8, 2011 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-21613255

RESUMO

Acute lymphoblastic leukemia of pre-B cells (pre-B ALL) is the most frequent form of leukemia affecting children in Western countries. Evidence is accumulating that genetic factors play an important role in conferring susceptibility/resistance to leukemia in children. In this regard, activating killer-cell immunoglobulin-like receptor (KIR) genes are of particular interest. Humans may inherit different numbers of the 6 distinct activating KIR genes. Little is known about the impact of this genetic variation on the innate susceptibility or resistance of humans to the development of B-ALL. We addressed this issue by performing a case-control study in Canadian children of white origin. Our results show that harboring activating KIR genes is associated with reduced risk for developing B-ALL in these children. Of the 6 activating KIR genes, KIR2DS2 was maximally associated with decreased risk for the disease (P = 1.14 × 10(-7)). Furthermore, our results showed that inheritance of a higher number of activating KIR genes was associated with significant reductions in risk for ALL in children. These results were also consistent across different ALL phenotypes, which included children with pre-T cell ALL. Our study provides novel insights concerning the pathogenesis of childhood leukemia in white children and has implications for the development of new immunotherapies for this cancer.


Assuntos
Leucemia/genética , Receptores KIR/genética , Idade de Início , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Lactente , Recém-Nascido , Leucemia/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptores KIR/fisiologia
16.
Isr Med Assoc J ; 13(3): 161-5, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21608337

RESUMO

BACKGROUND: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia. OBJECTIVES: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999-2006. METHODS: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL-BFM-95 protocol. RESULTS: At a median follow-up of 4 years (range 1-9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five patients (13.5%) relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA). CONCLUSIONS: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Adolescente , Criança , Pré-Escolar , Humanos , Israel , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/radioterapia , Estudos Retrospectivos , Sociedades Médicas , Análise de Sobrevida , Adulto Jovem
17.
DNA Cell Biol ; 30(10): 777-82, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21476947

RESUMO

Recent findings suggest that CD14 may play a role in tumor development. Previous case-control studies have revealed that CD14 -260C/T and -651 C/T polymorphisms contribute to the risk of human diseases. However, the relationship between these two functional polymorphisms and susceptibility to acute lymphoblastic leukemia (ALL) has not been explored. In this study, we performed a case-control study in a Chinese population. We found that an increased risk of ALL was associated with the -260 TT (odds ratio [OR]=1.85, 95% confidence interval [CI]=1.26-2.63) genotype compared with the CT or CC genotype. No significant association was found between -651 CC genotype and ALL (OR=1.13, 95% CI=0.77-1.69). Moreover, the increased risk was only associated with the -260 TT genotype in B-ALL (OR=1.99, 95% CI=1.34-3.01) but not in T-ALL (OR=1.48, 95% CI=0.79-2.84). The findings suggest that CD14-260C/T polymorphism can contribute to B-ALL risk in a Chinese population.


Assuntos
Povo Asiático/genética , Estudos de Associação Genética , Receptores de Lipopolissacarídeos/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Regiões Promotoras Genéticas , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , China , Impressões Digitais de DNA , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Fatores de Risco
19.
Rev Panam Salud Publica ; 27(1): 17-22, 2010 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-20209227

RESUMO

OBJECTIVE: To determine the prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection among patients with lymphoproliferative disorders, as well as among their family members and sexual contacts, at two sentinel sites in Cuba. METHODS: An analysis was conducted of all the patients with a presumptive diagnosis of hematological malignancies seen by the hematology departments of the Hospital Hermanos Ameijeiras (HHA), City of Havana, and the Hospital Provincial Comandante Faustino Pérez (HPCFP), Matanza, Cuba, in January 1996-January 1997. HTLV-I seropositivity was determined by ELISA and Western Blot, and infection was confirmed by polymerase chain reaction. The positive patients' family members and sexual contacts were also assessed. The Z-test was used to compare proportions. RESULTS: Seroprevalence of HTLV-I infection in patients with lymphoproliferative disorders was 0.4% higher at the HPCFP than at the HHA (6.1% versus 0.2%, P<0.001). There were no significant differences in prevalence by age, sex, or skin color. Of the 53 family members and sexual contacts studied, 8 (15.1%) were positive for HTLV-I infection. CONCLUSION: The prevalence of HTLV-I in the study group was higher than previously found in Cuba. The value of seroepidemiological surveillance through sentinel sites was confirmed.


Assuntos
Infecções por HTLV-I/epidemiologia , Neoplasias Hematológicas/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Transtornos Linfoproliferativos/epidemiologia , Western Blotting , Busca de Comunicante , Cuba/epidemiologia , DNA Viral/sangue , Ensaio de Imunoadsorção Enzimática , Saúde da Família , Anticorpos Anti-HTLV-I/sangue , Neoplasias Hematológicas/virologia , Humanos , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Vigilância da População , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/virologia , Prevalência , Estudos Soroepidemiológicos , Parceiros Sexuais
20.
J Pediatr Oncol Nurs ; 27(3): 164-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20164246

RESUMO

The authors studied pediatric patients with B-precursor acute lymphocytic leukemia (ALL) to determine whether Mississippi's gender incidences correlate with national statistics. Furthermore, data on gender incidences in each of the risk categories of low, standard, and high were collected. A retrospective chart review was performed of pediatric B-precursor ALL patients diagnosed at the Children's Cancer Clinic at the University of Mississippi Medical Center from 1995 to 2005. The gender incidences in Mississippi were found to be comparable with the national average for ALL (1.34:1 vs 1.3:1) overall. However, the national average includes T-cell ALL, which is known to be significantly more prevalent in boys. Of greater significance, boys were noted to present with high-risk B-precursor ALL 4 times more than girls, suggesting the need for further investigation into possible causes of this phenomenon.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia , Centros Médicos Acadêmicos , Viés , Causalidade , Distribuição de Qui-Quadrado , Criança , Feminino , Humanos , Incidência , Masculino , Mississippi/epidemiologia , Vigilância da População , Leucemia-Linfoma Linfoblástico de Células Precursoras B/classificação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Prevalência , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Estados Unidos/epidemiologia
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