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Chronic lymphocitic leukemia - Top 30 Publications

Advances in chronic lymphocytic leukemia pharmacotherapy.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease that affects B lymphocytes in most cases. Leukemic lymphocytes have prolonged longevity, defined by resistance to apoptosis. These cells can accumulate in peripheral blood, bone marrow, and solid lymphoid organs. CLL may be indolent or aggressive and has a range of prognostic factors such as expression of CD38 and ZAP-70, immunophenotypic and cytogenetic changes, imbalanced apoptosis proteins, and others. Although CLL has a low mortality rate, this disease is generally not considered curable until today. CLL treatment involves alkylating agents and glucocorticoids, purine analogs, monoclonal antibody therapies, and bone marrow transplantation. In recent decades, new drugs have appeared focusing on new targets and specific molecules, such as the BCR receptor, Bruton's tyrosine kinase, phosphatidylinositol 3-kinase, spleen tyrosine kinase, apoptosis proteins and microRNAs. The most appropriate treatment for CLL is one that involves in its protocol a combination of drugs according to the prognostic factors presented by each patient. In this sense, treatment individualization is essential. This article examines standard treatments for CLL and explores new treatments and potential new targets, as well as schematic protocols to understand where we are, how the treatment has evolved, and the advantages and disadvantages of new targets for CLL therapy.

Acquired disseminated superficial porokeratosis in a patient affected by chronic lymphocitic leukemia.

Plasma matrix metalloprotease 9 correlates with blood lymphocytosis, leukemic cell invasiveness, and prognosis in B-cell chronic lymphocytic leukemia.

The complex biology underlying chronic lymphocytic leukemia cell migration and tissue invasiveness is not yet completely understood and might provide novel predictive markers and therapeutic targets. A total of 36 patients out of treatment from at least 3 months were enrolled and followed up for a median period of 44.2 months (range: 4.4-99.2). Matrix metalloprotease 9 and tissue inhibitor of metalloproteases 1 plasma levels and production/release from lymphoid cells were measured by zymography and enzyme-linked immunosorbent assay (ELISA) analysis. Malignant and normal lymphocyte mobility and matrix-degradation capability were studied using a Boyden chamber system, with and without autologous plasma. Free matrix metalloprotease 9 plasma levels were related with blood lymphocytosis, especially in more advanced stages (p = 0.003), and higher concentrations were associated with an increased disease progression risk (hazard ratio = 9.0, 95% confidence interval = 1.5-13.8). Leukemic cells expressed and secreted very little matrix metalloprotease 9. On the contrary, normal lymphocytes derived from the same leukemic patients showed matrix metalloprotease 9 intracellular levels that were lower in subjects with higher blood lymphocytosis (p = 0.024) and more advanced stages (p = 0.03); the released quantities were inversely associated with matrix metalloprotease 9 plasma concentrations (p = 0.035). Leukemic cells had a reduced spontaneous mobility and matrix-degradation capability that were stimulated by autologous plasma (p = 0.001) and normal lymphocytes (p = 0.005), respectively. Matrix metalloprotease 9 affected cell invasiveness depending on concentration and disease stage. In conclusion, chronic lymphocytic leukemia cells have a reduced mobility, matrix-degradation capability, and matrix metalloprotease 9 production compared to their own autologous normal lymphocytes. They are exposed to matrix metalloprotease 9 of prevalently systemic origin whose higher levels are associated with both leukemic and normal lymphocyte accumulation in the peripheral blood and have a negative prognostic value.

Role of ZNF224 in cell growth and chemoresistance of chronic lymphocitic leukemia.

Chronic lymphocytic leukaemia (CLL) is associated with apoptosis resistance and defective control of cell growth. Our study describes for the first time a critical role in CLL for the KRAB-zinc finger protein ZNF224. High ZNF224 transcript levels were detected in CLL patients with respect to control cells. Moreover, ZNF224 expression was significantly lowered after conventional chemotherapy treatment in a subset of CLL patients. By in vitro experiments we confirmed that ZNF224 expression is suppressed by fludarabine and demonstrated that ZNF224 is involved in apoptosis resistance in CLL cells. Moreover, we showed that ZNF224 positively modulates cyclin D3 gene expression. Consistently, we observed that alteration of ZNF224 expression leads to defects in cell cycle control. All together, our results strongly suggest that in CLL cells high expression level of ZNF224 can lead to inappropriate cell growth and apoptosis resistance, thus contributing to CLL progression. Targeting ZNF224 could thus improve CLL response to therapy.

Cutaneous manifestations of leukemia.

To describe the type and frequency of cutaneous manifestations of leukemia.

New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.

Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

Hodgkin's lymphoma variant of Richter's syndrome.

Chronic lymphocytic leukemia/small lymphocitic lymphoma (CLL/SLL) is low-grade malignant lymphoprolipheration, that has tendency to convert to a higher-grade neoplasm over time. More common is the development of a diffuse large cell lymphoma or transformation into prolymphocytic cell population. In rare cases, 0.1-0.5% of patients develop multiple myeloma or Hodgkin's disease. We present 65-year-old female with Hodgkin's variant of Richter's syndrome. On the basis of clinical simptoms, cytological, hystological and immunohistological finding in April 2008 CLL/SLL were diagnosed. The patient was treated with 8 courses of R-CHOP. After 10 months, FNA of the one of the enlarged lymph node on the neck was performed. The diagnosis was Hodgkin's disease. Immuno-hystological studies of the lymph node was consistent with type I Hodgkin's type of Richter's syndrome. Patient was treated with 3 courses of ABVD and radiotherapy.

An unusual pathological finding of chronic lymphocitic leukemia and adenocarcinoma of the prostate after transurethral resection for complete urinary retention: case report.

We describe a patient who underwent transurethral resection of the prostate for urinary obstructive symptoms and had histological findings of adenocarcinoma of the prostate with prostatic localization of chronic lymphocitic leukemia (CLL). The contemporary presence of CLL, adenocarcinoma of the prostate and residual prostatic gland after transurethral resection has never been reported before and the authors illustrate how they managed this unusual patient.

Tumoral collision: cancer metastases within a second neoplasm.

A case report of epithelial carcinoma of the inferior lip which spread in cervical lymph nodes previously affected by a chronic lymphocitic leukaemia, is presented. The coexistence of both histological findings in some of the nodes (collision tumor) is remarked. We have made a review of the scanty literature about metastases on second tumors and compared and commented those features.

Evaluation of carcinoembryonic antigen (CEA) in patients with neoplasms and hematologic diseases.

Carcinoembryonic antigen (CEA), a oncofetal glicoprotein, has been regarded as specific marker for colorectal cancer initially and restricted to the significance of tumor-associated antigen afterwards. Circulating CEA levels were determined in 47 patients with hematologic malignancies, resulting elevated in 10 (21%). The highest values had been discovered in a chronic lymphocitic leukemia complicated by primary hepatoma, causing the problem of the role played by the second tumor, likewise to another CEA-positive patient with the association "Hodgkin's disease-pancreatic carcinoma". The CEA employment had not been particularly satisfactory in the therapeutic monitoring and in the early detection of the relapses, in opposition to the results referred in the colorectal, mammary and bronchogenic carcinoma.