RESUMEN
AIMS: To report the clinicopathological findings of 21 cases of primary nodal marginal zone B-cell lymphoma (NMZL). NMZL is a recently characterized lymphoma and few series have been published. METHODS AND RESULTS: The clinical data were characteristic of a disseminated disease at presentation: presence of peripheral and abdominal lymph nodes, bone marrow involvement (62%), disease stage III and IV (76%), elevated lactate dehydrogenase (LDH) (48%). Other features included peripheral blood involvement (23%), anaemia (24%), thrombocytopenia (10%) and presence of serum M component (33%), while the previously reported association with hepatitis C virus and cryoglobulinaemia was not found. Relapses were frequent but the majority of patients receiving chemotherapy had a good initial response. Morphological features were heterogeneous and there were some differences compared with other marginal zone B-cell lymphomas (MZL). Pure monocytoid B-cell lymphomas were rare (10%) but a minor component of monocytoid B cell was observed more frequently (23%). Plasmacytoid or plasmacytic differentiation was a very common feature (61%). Large cells and a high mitotic count were also frequent (57%). CONCLUSION: NMZL can be distinguished from splenic MZL and extranodal MZL by its aggressive morphology and disseminated disease at presentation.
Asunto(s)
Linfoma de Células B/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD20/análisis , Médula Ósea/patología , Proteínas de Unión al ADN/análisis , Femenino , Reordenamiento Génico de Cadena Pesada de Linfocito B/genética , Humanos , Inmunohistoquímica , Cariotipificación , Ganglios Linfáticos/patología , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-6 , Análisis de Supervivencia , Translocación GenéticaRESUMEN
The purpose of this study was to document the frequency and distribution of karyotypic changes present at diagnosis in 103 non-MALT marginal zone cell lymphoma (MZL) patients. This cytogenetic analysis of a large cohort extends previous observations and allows the identification of new cytogenetic features. Abnormalities identified in more than 15% of patients included +3/+3q (37%), 7q deletions (31%), +18/+18q (28%), 6q deletions (19%), +12/+12q (15%) and 8p deletions (15%). Trisomy 3/3q, 7q deletions, +18 and +12 were seen in different combinations in more than 30% of patients in comparison to 2% in lymphocytic lymphomas/chronic lymphocytic leukemias, 1% in mantle cell lymphomas and 7% in follicular lymphomas. The marked propensity of these abnormalities to be recurrently associated with the same tumoral clone of individual karyotypes allowed the delineation of a cytogenetic profile that may help to distinguish non-MALT MZL among other mature B-cell neoplasms. If +3/3q, +12/+12q, and 6q, 7q and 8p deletions were significantly associated with clinical prognostic factors previously reported to influence survival and time to progression, patients displaying these abnormalities did not experience a significantly shorter time to progression.
Asunto(s)
Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Adulto , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Estudios de Cohortes , Análisis Citogenético , Progresión de la Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Linfoma de Células B/clasificación , Linfoma de Células B de la Zona Marginal/clasificación , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma Folicular/diagnóstico , Linfoma Folicular/genética , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/genética , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity of unknown etiology characterized by a polyclonal expansion of B-lymphocytes with typical bilobulated forms, elevated serum IgM, and an additional isochromosome for the long arm of chromosome 3 as the sole change. In the present study, we investigated four cases of PPBL by means of conventional cytogenetic analysis and FISH. In all patients, the polyclonality of the lymphoproliferation was demonstrated by immunophenotypic studies, and PCR analysis failed to demonstrate clonal IGH rearrangements in three evaluated cases. In two patients, in addition to +i(3)(q10), banding techniques identified unrelated clones with trisomy 3. FISH studies using a chromosome 3 long arm-specific probe provided evidence that all cases had both +i(3)(q10) and +3. To determine more precisely the distribution of the chromosomal abnormalities within the peripheral lymphocyte population, we investigated two of these cases using a technique of simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION). We demonstrated that both abnormalities were randomly distributed among the B-lymphocytes, independently of the kappa or lambda light chain isotype and the nuclear aspect. These data lead us to conclude that trisomy 3 represents, in addition to +i(3)(q10), another recurrent cytogenetic change in PPBL, suggesting that this lymphoproliferative disorder is associated with an increased frequency of chromosome 3 instability.
Asunto(s)
Linfocitos B/patología , Aberraciones Cromosómicas/genética , Cromosomas Humanos Par 3 , Linfocitosis/genética , Adulto , Linfocitos B/química , Trastornos de los Cromosomas , ADN de Neoplasias/análisis , Femenino , Humanos , Cadenas gamma de Inmunoglobulina/genética , Cadenas kappa de Inmunoglobulina/genética , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana EdadRESUMEN
Resistant variants of the human leukaemic line K562 were developed using selection with the deoxynucleoside analogues cytosine arabinoside, 2-chlorodeoxyadenosine, fludarabine and gemcitabine. The resistant lines displayed a high degree of cross resistance to all deoxynucleoside analogues, with little or no cross resistance to other agents. There was a profound accumulation defect of all nucleoside analogues in the resistant variants but no significant defect in nucleoside transport in any of the variants. 5' nucleotidase activity was strongly increased and deoxycytidine kinase activity was moderately reduced in all of the resistant variants, resulting in reduced accumulation of triphosphate analogues. In addition a deletion in one of the alleles of the deoxycytidine kinase was detected in the fludarabine-resistant line. Ribonucleotide reductase activity was found to be strongly increased in the gemcitabine-selected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line. Free nucleotide pools were increased in the 2-chlorodeoxyadenosine-selected line. There was no expression of the mdr1 gene by the resistant lines. Karyotypic analysis and FISH experiments using a 6q21 specific probe showed alterations in the 6(q16-q22) region which contains the 5'-nucleotidase gene. Early events in the activation and degradation of deoxynucleoside analogues appear to constitute common mechanisms of resistance to these compounds.
Asunto(s)
Antineoplásicos/uso terapéutico , Cladribina/uso terapéutico , Citarabina/uso terapéutico , Desoxicitidina/análogos & derivados , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Vidarabina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina Quinasa/metabolismo , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células K562 , Leucemia Eritroblástica Aguda/enzimología , Fenotipo , Vidarabina/uso terapéutico , GemcitabinaRESUMEN
Unbalanced translocations involving chromosome arm 17p, where the TP53 tumor suppressor gene localizes, are rarely described in chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), but recent use of molecular cytogenetic techniques have indicated a significant incidence of TP53 deletions, suggesting the involvement of chromosome 17p in these disorders. By conventional karyotype, we have identified unbalanced translocations involving 17p in 14 out of 123 (11%) CLL/SLL patients with clonal abnormalities. Cases were characterized by resistance to chemotherapy and a poor clinical outcome. The karyotypes presented a high incidence of complex rearrangements and 17p translocations were characterized by various partners. In 10 cases a centric fusion was assessed by fluorescent in situ hybridization (FISH) experiments using specific centromeric probes. The incidence of dicentric translocations in these series is therefore significantly higher than usually described, arising in up to 71% (10 out of 14 cases). In all cases, translocations led to a monosomy 17p and to a TP53 monoallelic deletion. The adverse clinical outcome confirms that structural abnormalities involving chromosome 17p are associated with disease progression in patients with chronic lymphoproliferative disorders.
Asunto(s)
Cromosomas Humanos Par 17 , Leucemia Linfocítica Crónica de Células B/genética , Linfoma de Células B/genética , Translocación Genética , Antineoplásicos/uso terapéutico , Enfermedad Crónica , Cósmidos , Sondas de ADN , ADN Satélite/genética , Supervivencia sin Enfermedad , Genes p53 , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Resultado del TratamientoRESUMEN
Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity characterized by a moderate but sustained lymphocytosis where some binucleated or bilobulated circulating forms constitute, even if they are not entirely specific, the cytological hallmark of the disease. An additional chromosome long arm i(3)(q10) has recently been reported as a recurrent cytogenetic aberration, contrasting with a usual polyclonal immunoglobulin expression. To determine more precisely the distribution of the chromosomal abnormality within the peripheral lymphocyte population and study the relationship between the +i(3)(q10) and the bilobulated character, we investigated three new cases of PPBL displaying the cytogenetic abnormality on the karyotype, using a technique of simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION). We demonstrated that the +i(3)(q10) was restricted to the B lymphocytes, independently of the kappa or lambda light chain isotype and was present in both bilobulated and non-bilobulated cells. Therefore it is likely that the cytogenetic abnormality occurs at an early stage of lymphocyte differentiation in a precursor cell already committed to the B-cell lineage, before any rearrangement of immunoglobulin genes has taken place.
Asunto(s)
Linfocitos B/patología , Cromosomas Humanos Par 3/genética , Linfocitosis/genética , Trisomía , Adulto , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Persona de Mediana EdadRESUMEN
Recent evidence has shown that rare cases of aggressive non-Hodgkin lymphomas (NHL) derive from cells belonging to the natural killer (NK) lymphocyte lineage and a new clinico pathologic entity has been proposed. Though well documented in B- and T-cell NHL, chromosome abnormalities are rare findings in NK-NHL and to date, no recurrent cytogenetic abnormality has been described. The present study reports the clinical data, cytogenetic and fluorescence in situ hybridization (FISH) analysis of a new case of typical NK-NHL characterized by a primary unbalanced translocation (X;18) (q13;p11). Recent data of X;autosome translocation in malignant lymphomas have proposed Xp22 and Xq28 as the location of NHL-related oncogenes. According to other published reports on the involvement of the Xq13 region in NHL and particularly in aggressive forms, we hypothesize the existence of additional putative lymphoma-associated oncogenes at the band Xq13.
Asunto(s)
Cromosomas Humanos Par 18 , Células Asesinas Naturales/inmunología , Linfoma no Hodgkin/genética , Translocación Genética , Cromosoma X , Adulto , Linaje de la Célula , Femenino , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Cariotipificación , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patologíaRESUMEN
We describe a new nonrandom rearrangement, dic(4;17)(p11;p11), which was identified in three patients with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). All three cases had in common atypical morphological features with a significant component of prolymphocytes, an unusual clinical outcome, and were refractory to chemotherapy. To further define the cytogenetic breakpoints, we investigated the cases by whole chromosome painting and fluorescence in situ hybridization (FISH) with centromeric probes. FISH analysis detected the same cytogenetic rearrangement in all patients, suggesting that the dic(4;17)(p11;p11) is a recurrent translocation in SLL/CLL. Moreover, FISH analysis showed a monoallelic deletion of the TP53 gene in all cases, suggesting a correlation with the aggressive course of the disease and the clinical outcome observed in these patients.