Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma.

It is well established that interleukin-6 (IL-6) is an essential growth factor for multiple myeloma (MM) and patients with increased IL-6 levels have a poor prognosis. In healthy subjects, the presence of the C allele at a polymorphic site (-174 G/C) of the IL-6 gene is related to low IL-6 levels. In view of the potential association of this particular polymorphism with IL-6 concentration, and the relevance of IL-6 in MM pathogenesis, the objective of the present study was to investigate the prevalence of IL-6 (-174 G/C) promoter polymorphism and its association with development of MM in Brazilian individuals. We investigated the prevalence of these alleles in 52 patients and 60 healthy subjects (matched by age, sex, and race) of a Brazilian population. Thirty patients were male (42.4%), 24 (46.2%) were white and the median age at diagnosis was 58.5 years (range: 28 to 84 years). To determine the IL-6 (-174 G/C) polymorphism, molecular analysis was performed by polymerase chain reaction followed by endonuclease restriction digestion. The genotype distributions observed in the group of patients were 4% CC, 42% GC and 54% GG. The C allele frequency was 0.25. These results were similar to the control group, suggesting no impact of this polymorphism on the susceptibility to MM.

Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma

It is well established that interleukin-6 (IL-6) is an essential growth factor for multiple myeloma (MM) and patients with increased IL-6 levels have a poor prognosis. In healthy subjects, the presence of the C allele at a polymorphic site (-174 G/C) of the IL-6 gene is related to low IL-6 levels. In view of the potential association of this particular polymorphism with IL-6 concentration, and the relevance of IL-6 in MM pathogenesis, the objective of the present study was to investigate the prevalence of IL-6 (-174 G/C) promoter polymorphism and its association with development of MM in Brazilian individuals. We investigated the prevalence of these alleles in 52 patients and 60 healthy subjects (matched by age, sex, and race) of a Brazilian population. Thirty patients were male (42.4 percent), 24 (46.2 percent) were white and the median age at diagnosis was 58.5 years (range: 28 to 84 years). To determine the IL-6 (-174 G/C) polymorphism, molecular analysis was performed by polymerase chain reaction followed by endonuclease restriction digestion. The genotype distributions observed in the group of patients were 4 percent CC, 42 percent GC and 54 percent GG. The C allele frequency was 0.25. These results were similar to the control group, suggesting no impact of this polymorphism on the susceptibility to MM.

Cutaneous T-cell lymphoma with HTLV-I infection: clinical overlap with adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a malignant proliferation of mature helper T lymphocytes,(1) and is caused by human T-lymphotropic virus type I (HTLV-I);(2) an HTLV-I infection endemic in the Caribbean, south-western Japan, South America and Africa.(3,4) Seroepidemiological studies suggest that it is also endemic in Brazil.(5) Although carriers of HTLV-I show polyclonal integration of virus in T lymphocytes, only patients with ATLL of various subtypes show monoclonal integration of HTLV-I in tumor cells.(6,7) Cutaneous T-cell lymphomas (CTCL) are a group of primary cutaneous lymphoproliferative diseases(8) with unknown etiology.(9) The two most common presentations of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS).(10-13) However, both CTCL categories can easily resemble ATLL. Therefore, in HTLV-I endemic areas, differentiation between ATLL and CTCL must be performed, as they have different prognoses and treatment approaches.(14).

Plasmablastic multiple myeloma is associated with increased vascular endothelial growth factor immunoexpression.

The biologic basis of the negative prognosis of plasmablastic myeloma is not fully understood. To determine whether histologically aggressive multiple myeloma (MM) is associated with a more angiogenic marrow environment, bone marrow samples from 50 recently diagnosed MM patients were evaluated. Twelve percent (6/50) of patients presented plasmablastic MM, and this feature correlated with moderate/strong intensity of vascular endothelial growth factor staining of plasma cells (P = 0.036). Although plasmablastic MM was not associated with increasing of microvessel density, this new evidence of increased expression of vascular endothelial growth factor on plasmablasts suggests that the adverse prognosis conferred by plasmablastic disease may be due, at least in part, to secretion of this angiogenic cytokine, also suggesting that the subset of MM patients with plasmablastic features may derive particular benefit from antiangiogenic therapies.

Plasmablastic multiple myeloma is associated with increased vascular endothelial growth factor immunoexpression

The biologic basis of the negative prognosis of plasmablastic myeloma is not fully understood. To determine whether histologically aggressive multiple myeloma (MM) is associated with a more angiogenic marrow environment, bone marrow samples from 50 recently diagnosed MM patients were evaluated. Twelve percent (6/50) of patients presented plasmablastic MM, and this feature correlated with moderate/strong intensity of vascular endothelial growth factor staining of plasma cells (P = 0.036). Although plasmablastic MM was not associated with increasing of microvessel density, this new evidence of increased expression of vascular endothelial growth factor on plasmablasts suggests that the adverse prognosis conferred by plasmablastic disease may be due, at least in part, to secretion of this angiogenic cytokine, also suggesting that the subset of MM patients with plasmablastic features may derive particular benefit from antiangiogenic therapies.

Importance of combined-modality therapy for primary bone lymphoma.

Primary bone lymphoma (PBL) is a rare entity and comprises about 5% of all extranodal non-Hodgkin's lymphomas (NHL) and 7% of all primary bone tumors. To date there is no consensus about the optimal treatment for PBL. We retrospectively reviewed all cases of PBL treated at Hospital São Paulo, Brazil, over a 10-year-period (January 1992-January 2002). Medical records of 7 patients with PBL were reviewed and information on age at diagnosis, sex, NHL clinical staging (CS), treatment and response to treatment were retrieved. Five patients (72%) received combined-modality therapy (CMT) and all of them are in complete remission (CR) with a median follow up of 19 months (ranging from 12 to 144 months). We conclude that PBL is a potentially curable malignancy and treatment should be undertaken in a multiprofessional approach, in order to provide the best support which probably has to include chemotherapy, radiotherapy and, for patients with IPI higher than 2, consolidation with stem-cell transplantation.

Granuloma letal da linha média: abordagem clínica e terapêutica de três casos / Lethal midline granuloma: clinical management of three cases

Objetivo. Relato de três casos do GLLM acompanhados pela Disciplina de Hematologia e Hemoterapia da Unifesp-EPM que tiveram boa resposta à terapêutica e evoluçao favorável. Métodos. Após confirmaçao histológica e histoquímica, os pacientes foram submetidos à tratamento quimio e radioterápico com boa resposta terapêutica. Resultados. Atualmente estes pacientes encontram-se em remissao total da doença, com sobrevida média de 45 meses. Conclusao. Levando-se em consideraçao nossa pequena experiência, acreditamos que o tratamento radioterápico e a abordagem quimioterápica inicial agressiva sao fundamentais para uma boa evoluçao deste tipo de linfoma.

Leucemia mielóide aguda Ph1-positivo de novo ou crise blástica de leucemia mielóide crônica? Análise molecular e evoluçäo clínica de um caso / Ph1-positive acute myeloid leukemia de novo or chronic myeloid leukemia? Molecular analysis and clinical evolution of a case

Os autores relatam um caso de leucemia mielóide aguda (LMA) que apresentava, ao diagnóstico, basofilia no sangue periférico e cariótipo com presença do cromossomo Filadélfia (Ph1). Após um ano de tratamento com quimioterapia intensiva e em fase de remissao clínica e hematológica, a análise molecular pela técnica da reaçao em cadeia da polimerase-trasncriptase reversa (RT-PCR) revelou presença de doença residual (rearranjo b2-a2). A seguir, o paciente apresentou primeira recidiva como LMA e, após a remissao, evoluiu com quadro hematológico sugestivo de leucemia mielóide crônica (LMC) em fase crônica. Após dez meses, apresentou nova recidiva da LMA. Os autores discutem a dificuldade do diagnóstico diferencial entre LMA Ph1-positivo de novo e crise blástica mielóide como primeira manifestaçao clínica da LMC, baseados nos aspectos clínicos e moleculares.

Prognostic significance of BCR-ABL rearrangement in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of a reciprocal translocation between chromosomes 9 and 22 in at least 95 per cent of cases. At the molecular level, this translocation results in the activation of the ABL oncogene of chromosome 9, which becomes contiguous with the 5'end of the BCR gene on chromosome 22. The breakpoint usually occurs between exons 2 and 3 (b2-a2 rearrangement), or 3 and 4 (b3-a2 rearrangement) of the major breakpoint cluster region (M-BCR) of the BCR gene. The aim of the present study was to characterize the type of BCR-ABL transcript in 32 patients with CML using the reverse transcriptase-polymerase chaim reaction (RT-PCR) and to determine if this type of rearrangement is related to the survival of the patients. Our results confirmed that RT-PCR is more sensitive than cytogenetic analysis for identifying the Philadelphia (Ph1) chromosome (96.9 per cent vs 79.3 per cent). The frequencies of b2-a2 and b3-a2 rearrangements were 28.1 per cent and 65.7 per cent, respectively. The survival of patients presenting the b2-a2 or the b3-a2 rearrangement was not significantly different (P = 0.27750). The data suggest that the type of transcript has no prognostic value for CML patients.