Clinical, hematological and cytogenetic profile in fibroblast growth factor receptor 1 rearranged hematoloymphoid malignancies

The background of this study is FGFR1 belongs to a family of four, high-affinity receptor tyrosine kinase and is a legitimate oncogene associated with uterine, cervical, prostate, bladder, colorectal and lung cancers. It is rarely concomitant in myeloid and lymphoid neoplasms but has an aggressive clinical course with a high mortality rate when present. Cytogenetic abnormalities involving the FGFR1 gene is most frequently observed in AML, MPN with eosinophilia, T-ALL and T-LBL with ZMYM2 gene being the most common fusion partner. Methods of this study was to authors report a series of 4 cases with FGFR1 rearrangements. Results is three patients presented as T-cell Lymphoblastic lymphoma (T-LBL) and one as mixed phenotype acute leukemia (MPAL). The T-LBL cases harboured the FGFR1/ ZMYM2 fusion and the MPAL case harbored the CNTRL/FGFR1 fusion as identified by conventional cytogenetics and confirmed by molecular studies. Conclusion is authors herewith describe the clinical, biochemical, molecular and cytogenetic features observed in these cases.

Detection of immunoglobulin and TCR gene rearrangements by PCR using BIOMED-2 multi-plex protocols in T lymphoblastie lymphoma and acute lymphoblastic leukemia / 临床与实验病理学杂志

Purpose To investigate the sensitivity of BIOMED-2 primer system in T lymphoblastic lymphoma ( T-LBL) and acute lym-phoblastic leukemia ( ALL) patients immunoglobulin ( Ig) and T-cell receptor ( TCR) gene rearrangement, and to analyze the co-rear-rangement pattern. Methods Amplification of rearranged Ig and TCR gene was performed in standard PCR in 35 T-LBL/ALL pa-tients. PCR products were analyzed by heteroduplex and polyacrylamide gel electrophoresis. Results 16 cases (45. 7%) of 35 sam-ples were detected to have TCR gene rearrangements, including 6 cases (37. 5%) of TCRβgene monoclonal rearrangements, 4 cases (25. 0%) of TCRγ gene monoclonal rearrangements, 3 cases (18. 8%) of TCRβ and TCRγ gene double rearrangements, 2 cases (12. 5%) of TCRδ gene monoclonal rearrangements and 1 case (6. 3%) of TCRγand TCRδgene double rearrangements were detec-ted. 4 cases (11. 4%) of 35 samples detected to have clonal immunoglobulin and TCR gene rearrangements. 11 cases (39. 3%) of 28 T-LBL patients were detected to have TCR gene rearrangements, 6 cases (85. 7%) of 7 T-ALL have TCR gene rearrangements. Con-clusions BIOMED-2 multiplex PCR analysis strategy is a useful technique in the T-LBL patients.

T- Lymphoblastic lymphoma in adults / Linfoma linfoblástico T dos adultos

Adult T-lymphoblastic lymphoma is rare and has a poor prognosis. In the 80s, following the introduction of sequential, intensified chemotherapy, complete remissions in the order of 75 percent-95 percent of treated patients, were achieved. However, several patients, namely those with advanced disease, continued to relapse either in remission or during maintenance therapy. Moreover, all these early studies were not able to detect any valuable prognostic index to predict the outcome. In an attempt to reduce the relapse rate, upfront autologous stem cell transplantation in patients in complete remission was introduced. The results obtained with this approach were quite homogeneous, indicating a probability of disease-free survival of about 65 percent-75 percent and an overall survival rate of 60 percent. Successive therapies designed since 2000 were able to obtain complete remissions of above 90 percent, with a relapse rate in the order of 30 percent and an overall survival comparable to that obtained with the transplant procedure. Yet, these studies were also unable to detect valuable prognostic factors predictive of the outcome. Moreover, no study on the biologic profile of the disease has been developed. To improve the prognosis of T-lymphoblastic lymphoma it seems necessary to create national registries to collect both clinical and biological data of all lymphoblastic lymphoma patients. In this way it will be possible to reach critical numbers of data with which valid statistical analysis may be performed that is able to detect factors influencing the outcome. Moreover, subsets of patients needing intensified procedures such as stem cell transplant may be detected at diagnosis.

O linfoma linfoblástico de célula T é raro e com prognóstico ruim. Após introdução de terapêutica quimioterápica seqüencial e intensificada, remissões completas passaram a ser obtidas em 75 por cento-95 por cento dos pacientes. Entretanto, muitos pacientes, particularmente aqueles com a chamada doença avançada, continuaram a recair tanto durante a terapia de indução como na manutenção. Além disso, todos estes estudos iniciais não foram capazes de detectar qualquer índice prognóstico capaz de prever a evolução dos pacientes. No sentido de reduzir as taxas de recidiva, o transplante autólogo de célula progenitora hematopoética em pacientes em remissão completa foi introduzido. Os resultados obtidos com esta abordagem foram bastante homogêneos, indicando uma probabilidade de sobrevida livre de doença de 65 por cento-75 por cento e uma sobrevida global de 60 por cento. Sucessivos tratamentos desenhados já nos anos 2000, foram capazes de obter remissões completas acima de 90 por cento, com taxas de recidivas da ordem de 30 por cento e uma sobrevida global comparável à obtida com o transplante. Ainda, estes estudos também não foram capazes de detectar fatores prognósticos relacionados à evolução válidos. Mais ainda, qualquer estudo com perfil biológico foi desenvolvido. Para melhorar o prognóstico do LLB-T parece ser necessário esforço multicêntrico, de caráter nacional ou internacional, para coletar dados clínicos e biológicos. Nesta linha, é possível alcançar número crítico de dados com valor estatístico que poderiam ser capazes de detectar fatores com influência prognóstica. Finalmente, grupos de pacientes necessitam ser identificados para selecionar aqueles que poderiam se beneficiar do transplante de célula progenitora hematopoética detectados ao diagnóstico.