Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação Puntual , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-abl/genética , Adulto , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/genética , Humanos , Masculino , Inibidores de Proteínas Quinases/farmacologiaAssuntos
Janus Quinase 2/genética , Prurido/patologia , Água/efeitos adversos , Programas de Triagem Diagnóstica , Eritropoetina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Policitemia Vera/complicações , Policitemia Vera/diagnóstico , Policitemia Vera/genética , Policitemia Vera/patologia , Prurido/etiologia , Estudos RetrospectivosAssuntos
Calreticulina/genética , Mutação , Inibidores da Agregação Plaquetária/uso terapêutico , Quinazolinas/uso terapêutico , Trombocitemia Essencial/tratamento farmacológico , Trombocitemia Essencial/genética , Idoso , Alelos , Humanos , Masculino , Contagem de Plaquetas , Trombocitemia Essencial/diagnósticoRESUMO
PURPOSE: Chronic neutrophilic leukemia is a rare form of myeloproliferative neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of patients harbor somatic mutations of CSF3R gene and are potentially amenable to targeted therapy with JAK inhibitors. The incidence and clinical significance of additional mutations requires clarification. MATERIALS AND METHODS: A next-generation sequencing approach for myeloid malignancy-associated mutations was applied to diagnostic and matched blast crisis samples from four chronic neutrophilic leukemia patients. RESULTS: Next-generation sequencing confirmed the CSF3R T618I in all patients with identification of concurrent SRSF2, SETBP1, NRAS and CBL mutations at diagnosis. At blast crisis, clonal evolution was evidenced by an increased CSF3R T618I allele frequency and by loss or acquisition of CBL and NRAS mutations. CONCLUSION: The diagnostic utility of a targeted next-generation sequencing approach was clearly demonstrated with the identification of additional mutations providing the potential for therapeutic stratification of chronic neutrophilic leukemia patients.
Assuntos
Crise Blástica/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leucemia Neutrofílica Crônica/genética , Leucemia Neutrofílica Crônica/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoAssuntos
Consenso , Técnicas de Diagnóstico Molecular/métodos , Transtornos Mieloproliferativos/genética , Análise Mutacional de DNA , Marcadores Genéticos/genética , Humanos , Irlanda , Janus Quinase 2/genética , Técnicas de Diagnóstico Molecular/normas , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/enzimologia , Guias de Prática Clínica como AssuntoAssuntos
Biomarcadores Tumorais/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Mutação de Sentido Incorreto , Receptores de Fator Estimulador de Colônias/genética , Aloenxertos , Sequência de Bases , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco , Fatores de TempoRESUMO
We report on a patient who developed donor-derived cutaneous T-cell lymphoma (CTCL) 4 years after successful treatment of chronic myeloid leukaemia with an allogeneic bone marrow transplant. The patient developed an eczematous rash unresponsive to topical therapy and immunosuppression. When CTCL was diagnosed in the recipient, his sibling donor had been attending his local dermatology unit with a maculosquamous rash, which proved subsequently to be mycosis fungoides. An identical pattern of donor and recipient clonality assessment and T-cell receptor gene sequencing indicated that the CTCL was probably transmitted in the bone marrow harvest. This suggests that CTCL cells circulate in the marrow at an early subclinical stage in this disease. This is the second case of donor-derived CTCL reported to date.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Micose Fungoide/etiologia , Neoplasias Cutâneas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Irmãos , Transplante Homólogo/efeitos adversosRESUMO
Hairy cell leukaemia (HCL) has distinct clinical, morphological and immunophenotypic features with no recurrent cytogenetic or molecular abnormalities reported until the recent description of the BRAF V600E mutation in patients with classical HCL. The incidence of this mutation was sought in 27 patients with either classical HCL or HCL variant by an allele-specific PCR approach and findings related to morphology, cytochemistry and immunophenotype. A high degree of correlation was noted between the presence of BRAF V600E and established diagnostic criteria in 26/27 patients with HCL/HCL variant. Detection of the BRAF V600E mutation is therefore a useful adjunct in the differential diagnosis of HCL and HCL variant and highlights the value of a multifaceted approach to the diagnosis of this malignancy.
Assuntos
Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Células da Medula Óssea/patologia , Diagnóstico Diferencial , Feminino , Variação Genética , Histocitoquímica , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Sequência de Aminoácidos , Sequência de Bases , Feminino , Humanos , Íntrons , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase em Tempo Real , Deleção de SequênciaAssuntos
Regulação Leucêmica da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Citocinas/genética , Adolescente , Adulto , Idoso , Feminino , Testes Genéticos , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
BACKGROUND: Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haematopoietic progenitor cells. Approximately half of all adult AML patients have a normal karyotype (NK-AML) and an intermediate risk prognosis. AIMS: To determine the incidence and prognostic significance of NPM1 and FLT3-ITD mutations in a population of patients with NK-AML. METHODS: FLT3-ITD and NPM1 mutation status was retrospectively sought in presentation samples from 44 NK-AML patients. RESULTS: FLT3-ITD and NPM1 mutations were detected in 45.5 and 54.5% of patients, respectively, allowing stratification according to genotype. CONCLUSIONS: FLT3-ITD and NPM1 mutation status can be defined in NK-AML. Prospective screening for these mutations is advocated in all NK-AML patients, as the genotype is of clinical importance when considering treatment options including stem cell transplantation.
Assuntos
Leucemia Mieloide Aguda/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Eletroforese em Gel de Ágar , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Prognóstico , Estudos Retrospectivos , Estudos Soroepidemiológicos , Cariótipo XYY , Adulto JovemAssuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Quimeras de Transplante , Benzamidas , Resistencia a Medicamentos Antineoplásicos/genética , Transplante de Células-Tronco Hematopoéticas , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Linfócitos , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
BACKGROUND: The chronic myeloproliferative disorders (MPD) are clonal haemopoietic stem cell disorders. AIMS: The incidence of JAK2 V617F mutation was sought in a population of patients with MPD. METHODS: The JAK2 V617 mutation status was determined in 79 patients with known MPD and 59 patients with features suggestive of MPD. RESULTS: The mutation was found in patients with polycythaemia vera, essential thrombocythaemia, idiopathic myelofibrosis and in patients with other chronic myeloproliferative disorders. Eight JAK2 V617F positive cases were identified amongst those patients with features suggestive of MPD. CONCLUSIONS: The incidence of the JAK2 V617F mutation in MPD patients is similar to that reported by other groups. The assay confirmed and refined the diagnosis of several patients with features indicative of MPD. We suggest screening for this mutation in all patients with known and suspected MPD as identification is valuable in classification and is a potential target for signal transduction therapy.
Assuntos
Janus Quinase 2/genética , Transtornos Mieloproliferativos/genética , Doença Crônica , Humanos , Mutação , Policitemia Vera/genética , Reação em Cadeia da Polimerase , Mielofibrose Primária/genética , Trombocitemia Essencial/genéticaRESUMO
Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder caused by mutations in one of seven known genes (FANCA,C,D2,E,F,G and BRCA2). Mutations in the FANCA gene are the most prevalent, accounting for two-thirds of FA cases. Affected individuals have greatly increased risks of acute myeloid leukemia (AML). This raises the question as to whether inherited or acquired mutations in FA genes might be involved in the development of sporadic AML. Quantitative fluorescent PCR was used to screen archival DNA from sporadic AML cases for FANCA deletions, which account for 40% of FANCA mutations in FA homozygotes. Four heterozygous deletions were found in 101 samples screened, which is 35-fold higher than the expected population frequency for germline FANCA deletions (P<0.0001). Sequencing FANCA in the AML samples with FANCA deletions did not detect mutations in the second allele and there was no evidence of epigenetic silencing by hypermethylation. However, real-time quantitative PCR analysis in these samples showed reduced expression of FANCA compared to nondeleted AML samples and to controls. These findings suggest that gene deletions and reduced expression of FANCA may be involved in the promotion of genetic instability in a subset of cases of sporadic AML.
