RESUMO
Diagnosis and treatment patients with lymphoma is still obe of the main problems in theoretical and clinical oncology. Observing increasing tendency of lymphoma incidence in Ukraine it should be noted that the disease is prevalent in young and working-age population. Therefore it is important to improve effectiveness of treatment in primary diagnosed non-Hodgkin lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/genética , Raios gama/uso terapêutico , Linfoma de Células B/terapia , Linfoma de Células T/terapia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adulto , Fatores Etários , Idoso , Biomarcadores Tumorais/metabolismo , Ciclofosfamida , Doxorrubicina , Feminino , Expressão Gênica , Humanos , Idarubicina , Imuno-Histoquímica , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Linfonodos/patologia , Linfonodos/efeitos da radiação , Linfoma de Células B/genética , Linfoma de Células B/mortalidade , Linfoma de Células B/patologia , Linfoma de Células T/genética , Linfoma de Células T/mortalidade , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Prednisolona , Prednisona , Proteína Quinase C beta/genética , Proteína Quinase C beta/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Análise de Sobrevida , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ucrânia , VincristinaRESUMO
Important characteristics of chronic lymphocytic leukaemia (CLL) cells are biased immunoglobulin variable heavy chain (IGHV) gene repertoire and expression of stereotyped B-cell receptors (BCRs); however, their prognostic value (in contrast to the impact of IGHV gene mutational status) is less clear. To evaluate the impact of separate IGHV gene usage and expression of stereotyped BCRs in CLL prognosis. Clinical data and IGHV gene configuration were analysed in 319 consecutive patients with CLL. We found that the majority of clinical parameters of patients were defined by IGHV mutational status. Our data also provided new evidence supporting the prognostic relevance of separate IGHV genes or stereotyped BCR in CLL, namely: (a) a restricted non-mutated (UM) IGHV gene repertoire in CLL patients with autoimmune haemolytic anaemia (AIHA) (more frequent expression of UM IGHV1-69, IGHV3-11 and IGHV4-59 genes, P = 0.001), a shorter period of AIHA development for expressors of these genes (P = 0.001) and a tendency towards expression of a stereotypic HCDR3 (P = 0.029), (b) a high incidence of second solid tumour development in IGHV3-21-expressing patients (P = 0.005) and (c) differences in overall survival (OS) of UM CLL patients depending on the BCR structure. Further research of specific IGHV gene usage and subsets of stereotyped BCRs in CLL may be helpful in more precise prediction of CLL prognosis in individual patients.
Assuntos
Rearranjo Gênico , Genes de Cadeia Pesada de Imunoglobulina , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Receptores de Antígenos de Linfócitos B/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcaloides de Berberina , Estudos de Coortes , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenantridinas , Prognóstico , Taxa de SobrevidaRESUMO
UNLABELLED: THE AIM of the study was to evaluate the frequency of IGHV3-21 gene usage and its clinical significance for patients with B-cell chronic lymphocytic leukemia (CLL) in Ukraine. PATIENTS AND METHODS: Immunoglobulin variable heavy chain (IGHV) gene repertoire was studied in 189 CLL patients using reverse transcribed polymerase chain reaction and direct sequence of amplified products. RESULTS: IGHV3-21 gene expression was found in 11 cases (5.8%), and its frequency was intermediate between Scandinavian (11.7%) and Mediterranean CLL (2.9%) cohorts. The most of cases (9 of 11) belonged to subset with heterogeneous HCDR3 (heteroHCDR3 subset), and only 2 cases--to subset with classical short ARDANGMDV motif (homHCDR3 subset). Six IGHV3-21 cases were mutated and 5 cases were unmutated. All unmutated cases (all were from heteroHCDR3 subset) had similarity of their HCDR3s with previously published sequences. The differences in overall (OS), progression-free (PFS) and treatment-free survival (TFS) for IGHV3-21 positive patients in comparison with CLL patients expressing the other IGHV genes were statistically insignificant. These survival parameters were comparable also for CLL patients with mutated IGHV3-21 gene usage and expression the others mutated IGHV genes. But remarkable feature of IGHV3-21 expressing patients was high incidence of solid tumors. They have developed in 4 IGHV3-21 positive cases (36.4%) and in 10 cases with expression of the others IGHV genes (5.6%, p=0.0002). Furthermore, in small group of 6 patients with mutated IGHV3-21 gene expression, 3 patients had solid tumors and one underwent Richter transformation. Unmutated IGHV3-21 gene expressed patients had worse OS and PFS in comparison with CLL patients that expressed the others unmutated IGHV genes. CONCLUSION: Presented data are in agreement with the opinion about negative prognostic significance of IGHV3-21 gene expression regardless its mutation status. IGHV3-21 expression was associated with development of secondary solid tumors. Revealed high level of homology in heteroHDR3s subset might suggest about possible antigenic influence also, in addition to homHCDR3 subset that was proposed earlier.
Assuntos
Expressão Gênica , Genes de Cadeia Pesada de Imunoglobulina , Leucemia Linfocítica Crônica de Células B/genética , Segunda Neoplasia Primária/genética , Adulto , Idoso , Sequência de Aminoácidos , Feminino , Citometria de Fluxo , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Humanos , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , UcrâniaRESUMO
AIM: The aim of this study was to evaluate significance of VH mutation status for prognosis of B-cell chronic lymphocytic leukemia (B-CLL) patients in comparison with other prognostic markers. MATERIALS AND METHODS: The VH mutation status was evaluated in 43 B-CLL patients by RT-PCR amplification and nucleotide sequencing, and CD38 expression - by two-color FACS analysis. The prognostic influence of VH mutation rate and CD38 expression level was tested by different statistical methods. RESULTS: The increasing number of advanced cases over the follow-up period, shorter median time from diagnosis to start of second line therapy, worse response to fludarabine treatment, poor survival for early stages B-CLL were found in unmutated versus mutated CLL patients. The significance of CD38 expression for CLL prognosis was revealed as predictor for response for fludarabine treatment and time of progression in advanced stages. The correlation between CD38 expression and VH mutation status was not found. CONCLUSION: Simultaneous determination of VH mutation status and CD38 expression may be helpful for prediction of CLL prognosis.