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CONTEXT: The fusion gene BCR-ABL1 is present in at least the fourth part of B-cell acute lymphoblastic leukemia adult cases. Patients with this fusion gene are candidates to tyrosine kinase inhibitors treatment, and the response to this therapy can be measure by quantification of BCR-ABL1 transcripts. Some patients relapse because the presence of mutations in the tyrosine kinase domain of BCR-ABL1. CASE REPORT: This is a report of a patient with BCR-ABL1 who initially achieved molecular response with imatinib therapy, relapsing after fifteen months. The treatment was changed to dasatinib, but the patient doesn't achieve molecular response. Retrospectively, we analyzed the tyrosine kinase domain of BCR-ABL1 and we found three mutations (E459K, E255K and V299L). CONCLUSIONS: We conclude that gain of mutations during treatment with TKIs has strong impact in the progress of disease, being relevant the detection of BCR-ABL1 mutations in relapsed patients or in case of BCR-ABL1 persistence.

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Evaluar el efecto inmunomodulador sobre poblaciones linfocitarias, células dendríticas (DC), citoquinas Th1/Th2/Th17 (T-helper) e inflamatorias en el ámbito sistémico y/o en el microambiente tumoral de ratones con o sin melanoma. Materiales y métodos. Se obtuvieron muestras de sangre periférica y/o de tumores primarios de ratones con melanoma B16 tratados o no con un extracto hidroalcohólico de Uncaria tomentosa (UT) con 5,03% de alcaloides oxindólicos pentacíclicos (UT-POA) obtenido de la corteza de la planta. Todos los ensayos de medición de células y citoquinas fueron realizados por citometría de flujo. Resultados. UT-POA a nivel sistémico incrementa la relación CD4/CD8a (Cluster of Differenciation), mientras que la activación celular es inversamente proporcional; incrementa la proporción de DCm (DC mieloides); induce un perfil Th1 proinflamatorio y reduce la respuesta Th17. TNF-a (tumor necrosis factor alpha) y IL-17A (interleuquina) correlacionan positiva y negativamente con la relación CD4/CD8a. Conclusiones. El incremento de Th1 (TNF-a) puede tener como consecuencia el incremento de linfocitos CD4 o la activación de macrófagos M1. Aunque UT-POA muestra un incremento de DCm, este no es dosis-dependiente. La disminución de Th17 (IL-17A) puede favorecer el funcionamiento de los linfocitos CD8a. UT-POA muestra mejores efectos inmunomoduladores en el ámbito sistémico que intratumoral...

To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. Materials and methods: Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the plant. All cell assays and cytokine measurements were performed by flow cytometry. Results. UT-POA systemically increased CD4/CD8a relation while cell activation was inversely proportional; increased the proportion of DCm; induced a pro-inflammatory Th1 profile and reduced Th17 response. TNF-a and IL-17A positively and negatively correlated with CD4/CD8a relation. Conclusions. The increase of Th1 (TNF-a) may result in the increase of CD4 or M1 macrophage activation. Although UT-POA shows increased DCm, is not dose-dependent. Th17(IL-17A) decreased can support the function of CD8a lymphocytes. UT-POA shows better systemic immunomodulatory effects than intratumoral...

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OBJECTIVES: To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. MATERIALS AND METHODS: Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the plant. All cell assays and cytokine measurements were performed by flow cytometry. RESULTS: UT-POA systemically increased CD4/CD8a relation while cell activation was inversely proportional; increased the proportion of DCm; induced a pro-inflammatory Th1 profile and reduced Th17 response. TNF-α and IL-17A positively and negatively correlated with CD4/CD8a relation. CONCLUSIONS: The increase of Th1 (TNF-α) may result in the increase of CD4 or M1 macrophage activation. Although UT-POA shows increased DCm, is not dose-dependent. Th17(IL-17A) decreased can support the function of CD8a lymphocytes. UT-POA shows better systemic immunomodulatory effects than intratumoral.

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Objetivo. Determinar el efecto de un extracto hidroalcohólico de uña de gato, Uncaria tomentosa (UG) sobre célulasdendríticas (DC) de sangre periférica y la expresión de HLA-DR y CD86 en muestras de sangre periférica de individuos sanos tratadas con lipopolisacáridos (LPS). Materiales y métodos. El polvo de la corteza de UG se preparó como una decocción estéril a 30g/L por 30 minutos. Se obtuvo muestras de sangre periférica de individuos sanos. Las célulasmononucleares de sangre periférica (CMSP) fueron separadas por gradiente de centrifugación, pretratadas o no durante dos horas con distintas concentraciones de UG y estimuladas 24 h con LPS, luego fueron marcadas con anticuerpos monoclonales fluorescentes específicos para HLA-DR, Linaje tipo 1 (Lin1), CD11c y CD86 y preparadas para la citometría de flujo. Resultados. Comparando con el grupo de CMSP con LPS pero sin UG se observó, de maneradosis dependiente, una disminución en el porcentaje de DC mieloides (DCm) (p menor que 0,05) y una tendencia a incrementar el porcentaje de DC plasmacitoides (DCp). En las DCp se observó una disminución de la intensidad de fluorescencia media (IFM) de HLA-DR sólo a 500 y 1000 μg/mL de UG (p menor que 0,001); mientras que hubo un incremento de la IFM de CD86en todo el rango (p menor que 0,05). En DCm a las mismas concentraciones no se observó efecto de UG sobre la IFM de HLA-DR y CD86. Conclusiones. Este extracto estandarizado de UG tiende a incrementar el porcentaje de DCp y disminuye el porcentaje de DCm. UG no afecta la expresión de HLA-DR y CD86 en DCm. Este estudio demuestra que este extracto de UG favorece la activación/diferenciación de DCp, la cual participa en mecanismos de respuesta inmune adaptativa.

Objective. To determine the effect of an hydro-alcoholic extract of cat´s claw Uncaria tomentosa (UG) overlipopolysaccharides û treated dendritic cells (DC) and HLA-DR and CD86 molecules expression of peripheral bloodsamples obtained from healthy individuals. Materials and methods. Peripheral blood samples were collected from healthy individuals. Peripheral Blood Mononuclear Cells (PBMC) were isolated by centrifugation over density gradient, pre-treated with and without the addition of UG, and then stimulated for 24 h with lipopolysaccharides (LPS), then the cells were labelled with specific fluorescent monoclonal antibodies to HLA-DR, Linage type 1 (Lin1), CD11c and CD86 and prepared for flow. Results. Compared to PBMC with LPS but without UG group, we found a decrease of myeloid DC (mDC) percentage (p minor that 0.05) and a tendency to increase plasmacytoid DC (pDC) percentage, both in a dose-dependent manner. There was a decrease in media fluorescence intensity (MFI) of HLA-DR in DCp between 500 and 1000 μg/mL of CC (p minor that 0,001), but we found a increase in MFI of CD86 at all concentrations (p<0,05). There was no effect of UG overMFI of the HLA-DR or CD86 expression in mDC. Conclusions. UG showed a tendency to increase pDC percentage and decreased mDC percentage. UG did not affect the expression of CD86 and HLA-DR from mDC. This study demonstrates that UG promotes activation/differentiation of pDC, which has a demonstrated involvement in the adaptive immune response mechanisms.

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