Arkadiusz Macheta

Assessment of red blood cell distribution width as a prognostic marker in chronic lymphocytic leukemia

Red blood cell distribution width (RDW) is a quantitative measure of the variability in size of circulating erythrocytes. It was recently reported that RDW is a prognostic factor for infection diseases, cardiovascular and pulmonary diseases, as well as some neoplasms. Moreover, RDW is remarkably strong predictor of longevity, including all causes of death, for adults aged 45 years and older. To explain this occurrence it was proposed that persistent IGFs/mTOR signaling is one of the factors that play a role in affecting the RDW and mortality. The above observations induced us to analyze the prognostic role of RDW in chronic lymphocytic leukemia (CLL) being the most frequent type of adult leukemia in Western countries. The obtained results have shown that RDW may be considered as a potential CLL prognostic marker. Elevated RDW level at the moment of diagnosis was associated with advanced disease and presence of other poor prognostic factors. It is also connected with overall survival indicating shorter time in patients with elevated RDW. It is possible that the presently observed correlation between mortality and RDW of the CLL patients is affected by their metabolic (IGF-1/mTOR driven)- rather than chronological- aging. The patients with high level of RDW are expected to have an increased persistent level of IGF-1/mTOR signaling. Within the framework of personalized therapy, these CLL patients therefore would be expected to be more sensitive to the treatment with mTOR inhibitors.

Changes in T-cell subpopulations and cytokine network during early period of ibrutinib therapy in chronic lymphocytic leukemia patients: the significant decrease in T regulatory cells number

B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration. The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively. The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.

Deregulation of Apoptosis - Is it Still an Important Issue in Pathogenesis of Chronic Lymphocytic Leukemia?

Chronic lymphocytic leukemia (CLL), a clonal expansion of B CD5+ cells, is the most common type of adult leukemia in western countries. The accumulation of neoplastic B-cells is primarily caused by prolonged life-span of these cells due to deregulation of apoptosis, and only marginally due to a higher proliferation rate. In spite of numerous reports characterizing particular mechanisms of B-CLL cell apoptosis, still relatively little is known about the complex regulation of this process. Therefore, more detailed research is required to understand the complicated mechanisms and regulatory processes of apoptosis in neoplastic B lymphocytes.

Genetic methods in diagnosis of hematooncological disorders

The development of various analitic techniques like classical cytogenetics, molecular cytogenetics and molecular methods has greatly improved our ability to understand the basis of cancer development, that can be helpful in hematological diagnostics and treatment. Thus, improving these methods and raising the diagnostic standards remain of key importance in haematooncology. The influence of cytogenetic and biomolecular analysies on clinical decisions has increased considerably recently, but laboratory techniques have to be optimized to provide reliable results for the best patient care. The aim of this study is to present the basis of genetic diagnostic methods used in hematooncology and their role in clinical practice.

THE TECHNIQUE OF FLOW CYTOMETRY IN DIAGNOSTIC RESEARCH

Flow cytometry is a technology that simultaneously counts and then examines multiple physical and/or chemical characteristics of single particles, usually cells, as they flow in a fluid stream through a beam of light. The properties measured include a particle’s relative size, relative granularity or internal complexity, and relative fluo rescence intensity. These characteristics are determined using an optical-to-electronic coupling system that records how the cell scatters incident laser light and emits fluo rescence. One of the most significant applications is immunophenotyping of cells - the most important tool in diagnosis and monitoring haematological disorders, such as acute and chronic leukemia, lymphoma, monoclonal gammopathy, myelodisplastic and myeloproliferative diseases.

Assessment of micro RNAs expression in leukemic cells as prognostic markers in chronic lymphocytic leukemia: micro RNAs can predict survival in a course of the disease

Numerous genetic alterations predicting prognosis and clinical outcome are revealed recently in chronic lymphocytic leukemia (CLL). Among them the deregulated expression of micro RNAs that can induce tumor growth, or act as tumor suppressors seem to be of great importance. This study aimed to analyze the possible role of chosen micro RNAs as markers of prognosis in patients with CLL. We assessed the expression of miR-21, miR-34a, miR-181a, miR-199a/b and miR-221 in previously separated leukemic cells with the use of qRQ-PCR technique at the moment of diagnosis. The results were then analyzed in regards to presence of prognostic factors, clinical data and the end points like progression free survival (PFS), time to progression (TP) and overall survival time (OS). We detected significant correlations between expression of the analyzed micro RNAs and CLL prognostic markers particularly as far as miR-221 and miR-181a were concerned. The subsequent analysis revealed that high expression of miR-34a and miR-181a as well as low miR-21 expression indicated longer TTP, while miR-221 was predictor of OS. The obtained results prove the role of micro RNAs as CLL prognostic markers, particularly as factors predicting survival in a course of the disease.

Polish hematology on the Internet

Abstract The end of 20th and the beginning of 21st century have brought an intense development of the IT applications, without which people cannot imagine life. In the last years, the Internet has been playing more and more crucial role. It has become a valuable source of information for a big group of people, both patients and medical staff. Pharmaceutical syndicates, scientific units, magazines, medical clinics and departments, as well as individuals design their own websites. This article introduces a review of the most important websites about hematology.

[Acute promyelocytic leukemia--modern approach to disease pathogenesis and differentiation treatment].

During last decades acute promyelocytic leukemia, once considered the deadly disease, has evolved to the most treatable of all subtypes of acute myeloid leukemias. The intense clinical and basic research has led to a rational approach to treatment in which the use of the differentiating agent all-trans-retinoic acid has proven to be effective first-line therapy. Arsenic trioxide, used for relapsed disease, further improved the survival rate of patients. The classical model presented the therapeutic success as a result of over-coming of the differentiation block characteristic of neoplastic cells. However, the resent in vivo and ex vivo studies, seem to show that the induction of differentiation process is not required to cure acute promyelocytic leukemia. Rather than inducing differentiation, targeting clonogenic leukemia initiating cells or destroying PML-RARa fusion protein may represent a more effective therapeutic goal in this type of leukemia.

Znaczenie antygenu cd200 jako czynnika prognostycznego w nowotworach hematologicznych

STRESZCZENIE cząsteczka CD200, znana rowniez jako antygen OX2, nalezy do nadrodziny immunoglobulin, ma charakter glikoproteiny transblonowej typu i i jest kodowana przez gen znajdujący sie na chromosomie 3. ekspresje immunoglobuliny CD200 stwierdzono na wielu typach komorek, natomiast ekspresja jej receptora CD200R ograniczona jest do komorek linii mieloidalnej. opublikowane dotychczas badania potwierdzają, ze sygnaly dostarczone przez związanie sie CD200 z receptorem odgrywają wazną role w regulacji odporności przeciwnowotworowej, wlączając w to hamujący wplyw na odpowiedź immunologiczną T-komorkową. ekspresje CD200 stwierdzono na komorkach plazmatycznych u chorych na szpiczaka mnogiego i komorkach blastycznych chorych na ostrą bialaczke szpikową, istnieją takze doniesienia o jej wartości rokowniczej w przebiegu tych chorob. wzmozona ekspresja CD200 na komorkach nowotworowych jest związana ze zlym rokowaniem, prawdopodobnie w wyniku immunosupresyjnego dzialania na uklad odpornościowy gospodarza.