Cytokines and soluble HLA-G levels in bone marrow stroma and their association with the survival rate of patients exhibiting childhood T-cell acute lymphoblastic leukemia.

Leukemic cells can induce defective expression of soluble factors and change marrow cytokine profile, leading to aberrant cell signaling, cell fixation and cell proliferation in bone marrow. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disorder which accounts for 15% of pediatric ALL. To evaluate the contribution of immunological factors on T-ALL survival, we measured Th1, Th2, Th17 cytokines and soluble HLA-G (sHLA-G) levels in bone marrow from 32 Brazilian children at diagnosis (D0), after induction (D19) and after consolidation (D49) of the chemotherapy phase. Data were analyzed using non-parametric tests, and survival rates were evaluated by Kaplan-Meier method (log-rank test). TNF, IL-10 and IL-6 levels were increased at diagnosis compared to D19 and D49. IL-10 levels<4.57pg/mL at diagnosis were associated with increased survival rate, in presence of positive correlation between IL-2 and IL-17 levels. Increased survival rate was also associated with IFN-γ levels<1.17pg/mL at D49, with a positive correlation observed between IL-4 and IL-2 as well IL-4 and IL-17 levels. In contrast, worse survival rate was associated with IL-2, IL-4 and IL-10 levels imbalance. In addition, increased sHLA-G levels at diagnosis were associated with increased leukocyte count, a well-known factor for poor prognosis. In conclusion, cytokines and sHLA-G play an essential role in marrow T-ALL microenvironment during chemotherapy, especially the immunosuppressive cytokine IL-10 which can be used as biomarker of disease outcome, being also a potential target for novel T-ALL treatments.

Influence of aberrant myeloid expression on acute lymphoblastic leukemia in children and adolescents from Maranhão, Brazil.

The aim of this study was to evaluate myeloid expression in acute lymphoblastic leukemia (ALL) in children and adolescents who had been referred to the Oncology Department in a hospital in the State of Maranhão based on demographic, laboratory, and clinical data. Myeloid expression was evaluated in 65 patients under 18 years of age who were diagnosed with morphological, cytochemical, and immunophenotypes of ALL. Demographic, laboratory (hemogram), and clinical variables were obtained from medical records. The sample was divided into groups with and without anomalous myeloid expression to analyze the variables. Myeloid expression was observed in 49.2% of the sample. Platelet count was significantly lower in the group of children without aberrant myeloid expression (33,627 platelets/mm(3), P = 0.01). A total of 88.9% of children with B-cell ALL without myeloid expression showed less than 50,000 platelets/mm(3) (P = 0.01). Thus, platelet count may be an important parameter in the diagnosis of children with ALL without myeloid aberrant expression and may indicate a greater risk of bleeding during treatment in this group.

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.

Método de reação em cadeia por polimerase para a pesquisa de retrovírus em casos de linfomas não-Hodgkin de células T periféricas e paraparesias crurais espásticas / PCR methods for retrovirus search in cases of non-Hodgkin lynphoma of peripheral T-cells and crural spastic paraparesis

Partindo de dois oligonucleotídeos degenerados derivados de uma fração conservada da região pol de retrovírus conhecidos, foi pesquisada a presença de agente viral exógeno ou de uma seqüência endógena similar as retrovirais (ERV). A partir da amplificação do DNA pela técnica de PCR, foram testadas células mononucleares periféricas de 33 portadores de paraparesia crural espática de evolução crônica sem agente etiológico conhecido, produzindo um fragmento de aproximadamente 500 bp em 8 destas amostras...

CD44 Expression in T-cell lymphoblastic leukemia

1. CD44 is an adhesion molecule expressed by B and T lymphocytes that mediates cell attachment to extracellular matrix components and specific cell surface ligands. In normal process of T-cell development, CD44 can be implicated in homing of bone marrow-derived T-cell precursors into the thymus. In hematopoietic malignancies, CD44 and other adhesion molecules can mediate the behavior of neoplastic cells such as metastatic migration. In the leukemic process, CD44 and other adhesion molecules can mediate the behavior of neoplastic cell such as metastic migration. In the leukemic process, CD44 expression is correlated with increased numbers of circulating blasts and it is present at other sites such as the central nervous system. 2. In the present study, CD44 was investigated in lymphoblasts from 30 patients with T-cell lymphoblastic leukemia (T-ALL) and peripheral lymphocytes from 10 healthy individuals. CD44 expression was detected in 23 (77 per cent) of T-ALL cases studied and was correlated with clinical features such as mediatinal mass, adenomegaly, and infiltration of the central nervous system and other ortgans. Interestingly, CD44 expression in patient with tumor infiltration was higher than in patients with no tumor infiltration. 3. These data suggest that CD44 may be regarded as an additional marker for tumor expansion in T-cell leukemias

Infección por HTLV-I, leucemia de células T del adulto y factor con actividad de parathormona

La infección por el virus linfotrópico humano tipo I (HTLV-I) se ha asociado a la paraparesia espástica tropical (PET) y a la leucemia/linfoma de células T del adulto (ATL). Recientemete se demostró que los desordenes del metabolismo del calcio que acompañan la ATL son debidos a la secreción de un factor con actividad de parthormonas producido por los linfocitos infectados por el HTVL-I. Se presenta el caso de una paciente con anticuerpos contra el HTVL-I, anormalidades en el metabolismo del calcio y con parámetros que la clasifican en uno de los subtipos de ATL.