The hematology journal : the official journal of the European Haematology Association最新文献

Objective: To explore the possible effect of p27 gene expression on the proliferation and apoptosis of HL-60 and Raji cell lines.

Methods: The infections of HL-60 and Raji cells were performed by the adenovirus-mediated p27 gene transfection approach. The efficiency of Adp27 infection and the expression of p27 mRNA and protein were evaluated by X-gal staining, RT-PCR and flow cytometry. The proliferation and apoptosis of HL-60 and Raji cells were estimated by using trypan blue staining, MTT assay, Annexin V/PI and DNA ladder electrophoresis.

Results: The infection efficiency of HL-60 and Raji cells were 40.3 and 32%, respectively; RT-PCR and flow cytometry showed that there were significant expressions of p27 mRNA and protein of HL-60 and Raji cells infected by Adp27, while HL-60 cells themselves showed only faint p27 mRNA and protein, and Raji cells hardly presented p27 mRNA and protein. The strong proliferation inhibitions, which were in a time-dependent manner for HL-60 and Raji cells infected by Adp27, were indicated by cell growth curve and MTT assay. After 72 h infection of HL-60 and Raji cells by Adp27, the Annexin V+/PI- apoptotic cell rates were 46.9 and 35.7% respectively, which were significantly increased compared with control group (4.7 and 5.6% respectively). The typical DNA ladder bands were detectable in HL-60 and Raji cells after 48 h of Adp27 infection.

Conclusion: The infection of HL-60 and Raji cells by means of adenoviral vector-mediated p27 gene could evidently inhibit cellular proliferation and promote cell apoptosis, which would provide experimental evidence for gene therapy of leukemia/lymphoma using adenovirus-mediated p27 gene approach.

Primary hepatic lymphoma is a rare but well-defined lymphoma entity that often pursues an aggressive clinical course. Most cases have been described in hepatitis C virus (HCV)-related chronic liver disease patients. Although anthracycline-based chemotherapy has been reported to be highly effective, the best therapeutic strategy has not been defined yet. The prognosis is dismal especially in patients treated with chemotherapy alone or when an advanced liver disease is present. Herein, we describe a case of primary hepatic large B-cell non-Hodgkin's lymphoma, in a patient with HCV chronic infection. After a minor response with eight cycles of CHOP chemotherapy, a complete and sustained remission was obtained with alpha-interferon at the daily dose of 3 MU. HCV-RNA clearance pace from the blood almost paralleled the response of the lymphoma and both diseases went in remission within 1 year of therapy. The possible place of alpha-Interferon in the treatment of primary hepatic lymphoma is discussed.

The evaluation of bone disease in multiple myeloma (MM) by conventional radiology has low reproducibility. In the last decade, several serum and urine biochemical parameters, for evaluation of bone turnover, have become available. The present study was designed to explore the value of six bone remodelation markers. It was studied in a series of 176 newly diagnosed patients with monoclonal gammopathies (107 MM and 69 monoclonal gammopathies of unknown significance (MGUS)). As control groups we used 25 patients with benign osteoporosis (BO) and 32 healthy individuals (HI). The bone markers analyzed included: bone resorption markers (BRM) (total pyridinoline, total deoxypyridinoline, free deoxypyridinoline and C-terminal telopeptide of collagen I) and bone formation markers (BFM) (bone alkaline phosphatase (bAP) and osteocalcin (OC)). Serum or urinary levels of BRM were significantly higher in MM patients than in MGUS patients, BO patients or HI (P < 0.001, respectively). BRM were higher in MM patients with lytic lesions. However, only C-terminal telopeptide discriminated MM patients without bone lesions from MGUS patients. BFM did not show significant differences in the aforementioned comparisons, although a trend toward higher values of OC and lower values of bAP in patients with early bone affectation was observed. Ratios BRM/BFM that contained bAP exhibited differences that were most significant between the MM group and other entities, as well as between the different MM subgroups. In fact, the ratios BRM/bAP provided discrimination between the MM subgroup without lyses and MGUS group (P < 0.01). BRM and BFM, especially the ratios, are useful in the evaluation of bone lesions in patients with monoclonal gammopathies.

Clinical, hematological and morphological peripheral blood and bone marrow characteristics, in particular, megakaryopoiesis and bone marrow cellularity, reveal diagnostic clues and pathognomonic features, which enable a clear-cut distinction between essential thrombocythemia (ET), polycythemia vera (PV) and prefibrotic and fibrotic agnogenic myeloid metaplasia (AMM). The characteristic increase of enlarged mature megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or slightly increased cellular bone marrow represent the hallmark of ET. The characteristic increase and clustering of enlarged mature and pleiomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses are the specific diagnostic features of untreated PV. ET may precede PV for many years to more than one decade. Prefibrotic and fibrotic AMM appears to be a distinct dual proliferation of abnormal megakaryopoiesis and myelopoiesis. The histopathology of the bone marrow in prefibrotic and fibrotic AMM is dominated by atypical enlarged and immature megakaryocytes with cloud-like immature nuclei, which are not seen in ET and PV at diagnosis and during follow-up. Myelofibrosis is not a feature of ET at diagnosis and during long-term follow-up. Myelofibrosis, which is secondary to the megakaryocytic/granulocytic myeloproliferation, and extramedullary myeloid metaplasia constitute a prominent feature and usually progress more or less rapidly during the natural history of PV and AMM. Life expectancy is normal in ET, normal in the first and decreased in the second decade of follow-up in PV, but significantly shortened in thrombocythemia associated with prefibrotic AMM as well as in the various fibrotic stages of AMM. These clinical and pathological characteristics of the Ph-negative MPDs, by including bone marrow histopathology, enable a clear-cut distinction between ET, PV and prefibrotic and fibrotic AMM. The use of established and new biological markers of MPDs, like spontaneous EEC, PRV-1 gene expression etc, should be validated in large prospective multicenter studies of newly diagnosed and previously treated MPD patients using the proposed European clinical and pathological (ECP) criteria as the only gold standard available for the proper diagnosis and differential diagnosis of ET, PV and AMM.

Chronic lymphocytic leukemia (CLL) is the most common adult hematological malignancy in the Western world and predominantly affects the elderly. The disease encompasses a wide spectrum of clinical symptoms, which translate into variable prognosis and survival. The stratification of patients based on their clinical risk profile has been aided by the recognition of novel prognostic markers, for example, VH mutations and ZAP-70 expression, and this process is fundamental to assigning the most appropriate treatment strategy on an individual basis. Although CLL remains incurable with standard treatments, important progress in treatment has been made. The discovery of purine analogs such as fludarabine has led to significant improvements in remission rates and freedom from progression but, unfortunately, no significant prolongation in survival. With the success of newer therapeutic approaches, such as the monoclonal antibodies and stem cell transplantation, the focus of current therapy is on using these approaches in combination with fludarabine to produce high rates of molecular complete response, to eradicate minimal residual disease, and to lengthen survival. This paper provides an overview of CLL and discusses how recent therapeutic developments have changed the management of this form of leukemia.

The current study was aimed at investigating platelet function in MDS and its clinical significance. There were 23 patients with untreated MDS at presentation, including refractory anemia (RA), RA with ringed sideroblasts, RA and excess blasts and chronic myelomonocytic leukemia RAEBt. The mean platelet count was 167.9 x 109/L. Patients with a platelet count less than 70 x 109/l were excluded. The mean bleeding time (BT) was 2.7 min. Only four MDS patients had BT longer than the normal 1-4 min range. Platelet aggregation (PA) was studied with epinephrine (Epi), ADP, arachidonic acid (AA), ristocetin and collagen. Overall, 16 (70%) patients had PA abnormality, 65% had impaired Epi-induced PA, 57% demonstrated reduced ADP-induced PA. AA, ristocetin and collagen was decreased PA in 48, 22 and 17%, respectively. Five patients (22%) demonstrated spontaneous PA. Only seven patients (30%) were found to have normal PA with all five inducers. Six (26%) patients had spontaneous mild bleeding and all six bleeding MDS patients demonstrated at least one abnormal platelet function. The only bleeding patient with all five PA tests normal demonstrated prolonged BT. In the present study of 23 newly diagnosed MDS patients, PA abnormalities were relatively common, the BTs were usually normal, and bleedings were relatively uncommon and mild at platelet count between 70 and 397 x 109/l.