Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by serine/threonine protein phosphatase inhibitors.

To elucidate the roles of serine/threonine protein phosphatases type 1 (PP1) and type 2A (PP2A) in methylprednisolone-induced differentiation of HL60 cells into granulocytes and K562 cells into monocytes, we examined the effect of serine/threonine protein phosphatase inhibitors, okadaic acid and Cal-A on the proliferation/differentiation of HL60 and K562 cells. Okadaic acid and Cal-A augmented methylprednisolone induced granulocytic differentiation and cell death of HL60 cells and monocytic differentiation and cell death of K562 cells in different dose ranges, respectively. These data suggest an important role of PP1 and PP2A in the mechanism leading to differentiation of leukemic cells.

Incidence of aplastic anemia in Turkey: a hospital-based prospective multicentre study.

The incidence of aplastic anemia among hospitalized adult patients was prospectively determined in this first study in Turkey. New cases of aplastic anemia among patients 14 years and older who were admitted to the study centers were included in a 3 year survey. Seventy-three patients fulfilled the diagnostic criteria, yielding a mean annual incidence rate of 1.14 cases in 10(3) admissions. The male-to-female ratio of the cases (1.6:1) differed from the almost equal ratio of the larger population of Turkey. The median age was 30 years and females were younger at diagnosis. The age distribution of the cases was different from that of the population; showing two incidence peaks in both sexes. The majority of the patients (89%) had severe disease.

Two consecutive spontaneous regressions to chronic phase in a patient with blastic transformation of chronic myelogenous leukemia.

In this report, we present a patient with chronic myeloid leukemia (CML) in blastic phase who had two consecutive episodes of spontaneous regression back to chronic phase without chemotherapy. Although, spontaneous remission (SR) is well documented in acute leukemia, SR in CML blastic phase is extremely rare and to the best of our knowledge only one case has been reported in the world literature. The factors possibly related to this phenomenon are discussed.

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

UNLABELLED: The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. BACKGROUND: The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. PATIENTS AND METHODS: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. RESULTS: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. CONCLUSIONS: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Asecretory POEMS Syndrome with Widespread Osteosclerotic Lesions.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) is a rare disease and constitues 1-2% of plasma cell dyscrasia. Most of the patients have few sclerotic bone lesions and more than 90% of patients have serum and/or urinary M-protein. In this report, we present a patient with POEMS syndrome who had severe polyneuropathy and unusual widespread osteosclerotic lesions without M- rotein in serum and urine. According to our knowledge, this is the first case of asecretory POEMS syndrome with multipl sclerotic lesions and polyneuropathy. Our patient is still well and able to work actively 4 years after diagnosis with the treatment of 12 courses of VAD by reducing the vincristine dosage.

Fibrinolytic activity and platelet release reaction in essential hypertension.

The incidence of atherosclerotic and thromboembolic complications is quite high in hypertensive patients. Blood platelets and fibrinolytic activity may play an important role in the development of these complications. We investigated fibrinolytic activity and in vivo platelet release reaction in essential hypertension. Plasma levels of beta thromboglobulin (BTG), platelet factor-4 (PF4), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and plasminogen were determined in 36 essential hypertensive and 20 age and sex-matched control subjects. Plasma BTG levels were significantly higher in the hypertensive subjects than in controls (p < 0.05), whereas PF4 levels were similar for both groups suggesting an increase of in vivo platelet activity. PAI-1 antigen levels were found to be significantly higher in the hypertensive patients as compared to the control subjects (p < 0.01). On the other hand significant variations of t-PA antigen and plasminogen values were not observed in the two groups. These results suggest that essential hypertension is associated with decreased fibrinolytic activity and enhanced platelet activity as evidenced by high plasma levels of PAI-1 and BTG.

Mitoxantrone and standard dose cytosine arabinoside therapy in refractory or relapsed acute leukemia.

Thirty adult patients with relapsing or refractory acute leukemia were treated with mitoxantrone 10 mg/m2 daily by 20-min intravenous infusion for 5 days and cytosine arabinoside (Ara-C) 200 mg/m2 daily by continuous infusion for 5 days. Complete remission was obtained in 9 of 15 patients (60%) with acute myeloblastic leukemia (AML), with a mean duration of 6 months (range 2-12 months). Among 15 patients with acute lymphoblastic leukemia (ALL), complete remission was obtained in 5 patients (33.3%), with a mean duration of 2 months. Partial remission was achieved in 2 patients with AML and 1 patient with ALL. Myelosuppression developed in all patients following chemotherapy. Nonhematologic side effects consisted of nausea, vomiting, mild alopecia, stomatitis and transient hepatic dysfunction. No cardiopulmonary toxicity or neurotoxicity was observed. Our therapeutic responses are similar to those obtained with high-dose Ara-C and mitoxantrone but with less toxicity.

Up-regulation of serine/threonine protein phosphatase type 2A regulatory subunits during methylprednisolone-induced differentiation of leukaemic HL-60 cells.

Serine/threonine protein phosphatase 2A (PP2A) may play a role in leukaemic cell differentiation of the HL-60 myeloid leukaemic cell-line after methylprednisolone induction. We have investigated the specific enzyme activity and expression of catalytic and regulatory subunits of PP2A. The resulting specific enzyme activity and immunoblots showed an increase in enzyme activity and the expression of regulatory subunits after methylprednisolone treatment. There was no change in the expression of PP2A catalytic subunits. It is suggested that the effect of methylprednisolone on leukaemic differentiation may be the result of PP2A upregulation.