O valor da imunofenotipagem para o diagnóstico do Mieloma Múltiplo e na avaliação da doença residual mínima The value of immunofenotyping for the diagnosis of Multiple Myeloma and for the evaluation of minimal residual disease

Os plasmócitos normais podem ser diferenciados dos presentes no mieloma múltiplo por imunofenotipagem. Os normais são CD45+, CD19+, CD20+, CD38++, CD56-/fraco, CD138+, mIg-, cIg policlonal. Por outro lado, os plasmócitos do mieloma múltiplo são monoclonais (cIg) e aproximadamente 80% são CD19-CD56+ e 20% CD19-CD56-. O perfil na leucemia plasmocitária primária é semelhante ao do mieloma, embora a positividade para o CD56 ocorra em 45% dos casos. Na gamopatia monoclonal de causa indeterminada existe uma mistura de plasmócitos normais e neoplásicos, que têm perfil semelhante ao do mieloma múltiplo. A doença residual na medula é importante para estimar a resposta terapêutica e pode ser avaliada por citometria de fluxo e pela reação da polimerase em cadeia para o rearranjo da cadeia pesada da Ig. A citometria apresenta sensibilidade de 10-4 a 10-5, é realizada em aproximadamente duas horas e a sua aplicabilidade chega a 90%. O PCR qualitativo tem sensibilidade de 10-6 enquanto o quantitativo, 10-5. Em ambos, o tempo para a realização é maior (2-3 dias), com aplicabilidade de 75%.<br>Normal plasma cells can be differentiated from multiple myeloma by their immunophenotype. Normal cells are CD45+, CD19+, CD20+, CD38++, CD56-/dim, CD138+, mIg- and polyclonal cIg. On the other hand, with multiple myeloma, plasma cells are monoclonal (cIg) and approximately 80% are CD19- CD56+ and 20% CD19- CD56-. The profile in plasma cell leukemia is similar to myeloma, but the CD56 is positive in 45% of cases. In the monoclonal gammopathy of undetermined significance there is a mixture of normal and neoplastic plasma cells. Residual disease in bone marrow is important to determine the efficacy of treatment and can be evaluated by flow cytometry or polymerase chain reaction of rearranged heavy chains of Ig. Flow cytometry has a sensitivity of 10-4 to 10-5, is performed in 2-3 hours and is applicable in 90% of cases. Qualitative PCR has a sensitivity of 10-6 and quantitative PCR of 10-5. Both tests are performed in 2-3 days and their applicability is around 75%

Designlab4u: Journal

Designlab4u it´s a laboratory designed to immerse design students in real pedagogical work; social or research contexts to create a professionally laboratory capable of responding to design requests through innovative methodologies that enables students more competitive and more creative in design practice. Created in November 2016, this laboratory is characterized by a research space applied to the practice and teaching of Design. DesignLab4u is defined as a laboratory within the Lisbon Polytechnic Higher School of Education, which recreates the real working environment of an agency. This laboratory aims to provide students with the opportunity to collaborate on real projects, with community projection, generated in an immersive learning context, facilitating and fostering creativity, as well as the development of cultural and social enrichment activities. It is intended to prepare professionals capable of executing projects in the design area of different genres and formats. This laboratory currently has a multidisciplinary team consisting of current students taking the ESELx Visual Arts and Technology course, former students with a scientific scholarship and master students from other partner institutions.info:eu-repo/semantics/publishedVersio

The presence of CD56/CD16 in T-cell acute lymphoblastic leukaemia correlates with the expression of cytotoxic molecules and is associated with worse response to treatment

Some cases of T-cell acute lymphoblastic leukaemia (ALL) express markers found in natural-killer (NK) cells, such as CD56 and CD16. Out of 84 T-cell ALL cases diagnosed at our Institution, CD56 and/or CD16 was detected in 24 (28.5%), which we designated T/NK-ALL group. Clinical features, laboratory characteristics, survival and expression of cytotoxic molecules were compared in T/NK-ALL and T-ALL patients. Significant differences were observed regarding age (24.9 vs. 16.4 years in T/NK-ALL and T-ALL, respectively, P = 0.006) and platelet counts (177 x 10(9)/l vs. 75 x 10(9)/l in T/NK-ALL and T-ALL, respectively, P = 0.03). Immunophenotypic analysis demonstrated that CD34, CD45RA and CD33 were more expressed in T/NK-ALL patients, whereas CD8 and terminal deoxynucleotidyl transferase were more expressed in T-ALL patients (P < 0.05). The mean overall survival (863 vs. 1869 d, P = 0.02) and disease-free survival (855 vs. 2095 d, P = 0.002) were shorter in patients expressing CD56/CD16. However, multivariate analysis identified CD56/CD16 as an independent prognostic factor only for DFS. Cytotoxic molecules were highly expressed in T/NK-ALL compared to T-ALL. Perforin, granzyme B and TIA-1 were detected in 12/17, 4/17 and 7/24 T/NK-ALL patients and in 1/20, 0/20 and 1/20 T-ALL respectively (P < 0.001, P = 0.036 and P = 0.054). Therefore, the presence of CD56/CD16 was associated with distinct clinical features and expression of cytotoxic molecules in the blasts.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo`s (FAPESP)[05/58519-5]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo`s (FAPESP)[05/04296-5]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo`s (FAPESP)[02/11086-9

Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia

Loss-of-function mutations in telomerase complex genes can cause bone marrow failure, dyskeratosis congenita, and acquired aplastic anemia, both diseases that predispose to acute myeloid leukemia. Loss of telomerase function produces short telomeres, potentially resulting in chromosome recombination, end-to-end fusion, and recognition as damaged DNA. We investigated whether mutations in telomerase genes also occur in acute myeloid leukemia. We screened bone marrow samples from 133 consecutive patients with acute myeloid leukemia and 198 controls for variations in TERT and TERC genes. An additional 89 patients from a second cohort, selected based on cytogenetic status, and 528 controls were further examined for mutations. A third cohort of 372 patients and 384 controls were specifically tested for one TERT gene variant. In the first cohort, 11 patients carried missense TERT gene variants that were not present in controls (P < 0.0001); in the second cohort, TERT mutations were associated with trisomy 8 and inversion 16. Mutation germ-line origin was demonstrated in 5 patients from whom other tissues were available. Analysis of all 3 cohorts (n = 594) for the most common gene variant (A1062T) indicated a prevalence 3 times higher in patients than in controls (n = 1,110; P = 0.0009). Introduction of TERT mutants into telomerase-deficient cells resulted in loss of enzymatic activity by haploinsufficiency. Inherited mutations in TERT that reduce telomerase activity are risk factors for acute myeloid leukemia. We propose that short and dysfunctional telomeres limit normal stem cell proliferation and predispose for leukemia by selection of stem cells with defective DNA damage responses that are prone to genome instability

Increased expression of miR-221 is associated with shorter overall survival in T-cell acute lymphoid leukemia

Abstract Background CD56 expression has been associated with a poor prognosis in lymphoid neoplasms, including T-cell acute lymphoblastic leukemia (T-ALL). MicroRNAs (miRNAs) play an important role in lymphoid differentiation, and aberrant miRNA expression has been associated with treatment outcome in lymphoid malignancies. Here, we evaluated miRNA expression profiles in normal thymocytes, mature T-cells, and T-ALL samples with and without CD56 expression and correlated microRNA expression with treatment outcome. Methods The gene expression profile of 164 miRNAs were compared for T-ALL/CD56+ (n=12) and T-ALL/CD56- (n=36) patients by Real-Time Quantitative PCR. Based on this analysis, we decided to evaluate miR-221 and miR-374 expression in individual leukemic and normal samples. Results miR-221 and miR-374 were expressed at significantly higher levels in T-ALL/CD56+ than in T-ALL/CD56- cells and in leukemic blasts compared with normal thymocytes and peripheral blood (PB) T-cells. Age at diagnosis (15 or less vs grater than 15 years; HR: 2.19, 95% CI: 0.98-4.85; P=0.05), miR-221 expression level (median value as cut off in leukemic samples; HR: 3.17, 95% CI: 1.45-6.92; P=0.004), and the expression of CD56 (CD56- vs CD56+; HR: 2.99, 95% CI: 1.37-6.51; P=0.006) were predictive factors for shorter overall survival; whereas, only CD56 expression (HR: 2.73, 95% CI: 1.03-7.18; P=0.041) was associated with a shorter disease-free survival rate. Conclusions miR-221 is highly expressed in T-ALL and its expression level may be associated with a poorer prognosis

Increased expression of miR-221 is associated with shorter overall survival in T-cell acute lymphoid leukemia

Abstract Background CD56 expression has been associated with a poor prognosis in lymphoid neoplasms, including T-cell acute lymphoblastic leukemia (T-ALL). MicroRNAs (miRNAs) play an important role in lymphoid differentiation, and aberrant miRNA expression has been associated with treatment outcome in lymphoid malignancies. Here, we evaluated miRNA expression profiles in normal thymocytes, mature T-cells, and T-ALL samples with and without CD56 expression and correlated microRNA expression with treatment outcome. Methods The gene expression profile of 164 miRNAs were compared for T-ALL/CD56+ (n=12) and T-ALL/CD56- (n=36) patients by Real-Time Quantitative PCR. Based on this analysis, we decided to evaluate miR-221 and miR-374 expression in individual leukemic and normal samples. Results miR-221 and miR-374 were expressed at significantly higher levels in T-ALL/CD56+ than in T-ALL/CD56- cells and in leukemic blasts compared with normal thymocytes and peripheral blood (PB) T-cells. Age at diagnosis (15 or less vs grater than 15 years; HR: 2.19, 95% CI: 0.98-4.85; P=0.05), miR-221 expression level (median value as cut off in leukemic samples; HR: 3.17, 95% CI: 1.45-6.92; P=0.004), and the expression of CD56 (CD56- vs CD56+; HR: 2.99, 95% CI: 1.37-6.51; P=0.006) were predictive factors for shorter overall survival; whereas, only CD56 expression (HR: 2.73, 95% CI: 1.03-7.18; P=0.041) was associated with a shorter disease-free survival rate. Conclusions miR-221 is highly expressed in T-ALL and its expression level may be associated with a poorer prognosis