Flow Cytometric Immunobead Assay for Detection of BCR-ABL1 Fusion Proteins in Chronic Myleoid Leukemia: Comparison with FISH and PCR Techniques.

Chronic Myeloid Leukemia (CML) is characterized by a balanced translocation juxtaposing the Abelson (ABL) and breakpoint cluster region (BCR) genes. The resulting BCR-ABL1 oncogene leads to increased proliferation and survival of leukemic cells. Successful treatment of CML has been accompanied by steady improvements in our capacity to accurately and sensitively monitor therapy response.

Drug-related cardiotoxicity for the treatment of haematological malignancies in elderly.

Several publications have focused on the cardiotoxicity of specific classes of hematological therapeutic agents such as antracyclines and cyclofosfamide. Cardiotoxicity of cancer chemotherapeutics is a problem for patients of all ages, but it increases with age. Toxicity can also develop months after the last chemotherapy dose, and late reactions can be seen years later when they present as new-onset cardiomyopathy.

Relapsing or refractory idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: the role of rituximab.

Idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a rare disease responsive to treatment with plasma exchange (PE) but with a high percentage of relapse or refractory patients. A severe deficiency of ADAMTS-13 (<5% of normal activity), congenital or caused by an autoantibody, may be specific for TTP and it has been proposed that severe ADAMTS-13 deficiency now defines TTP. B cells play a key role in both the development and the perpetuation of autoimmunity, suggesting that B-cell depletion could be a valuable treatment approach for patients with idiopathic TTP-HUS.

Correlation between leukocytosis and thrombosis in Philadelphia-negative chronic myeloproliferative neoplasms.

The evidence that leukocytes may contribute to the pathogenesis of thrombosis in Chronic Myeloproliferative Neoplasms is increasing but not definitive. To further enforces whether an increased leukocyte count is associated with thrombosis and whether this effect can be modulated by cytoreductive therapy, we analyzed the clinical course of 187 patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) followed at two Italian Institutions over a period of 7 years. The association was measured at diagnosis or before thrombotic events: a multivariable analysis was carried out using data at baseline and time-dependent covariates.

[Serological screening for Leishmania infantum in asymptomatic blood donors and HIV+ patients living in an endemic area].

Visceral leishmaniasis (VL) is endemic in Sicily (48 new cases in 2004, of which nine were in Agrigento). In southern Europe between 25-70 per cent of adult VL cases are related to HIV infection. The HIV cases have a high risk (1.

Identification of a terphenyl derivative that blocks the cell cycle in the G0-G1 phase and induces differentiation in leukemia cells.

To further explore the SAR of resveratrol-related trans-stilbene derivatives, here we describe the synthesis of (a) a series of 3,5-dimethoxy analogues in which a variety of substituents were introduced at positions 2', 3', 4', and 5' of the stilbene scaffold and (b) a second group of derivatives (2-phenylnaphthalenes and terphenyls) that incorporate a phenyl ring as a bioisosteric replacement of the stilbene alkenyl bridge. We thoroughly characterized all of the new compounds with respect to their apoptosis-inducing activity and their effects on the cell cycle. One of the new derivatives, 13g, behaved differently from the others, as it was able to block the cell cycle in the G(0)-G(1) phase and also to induce differentiation in acute myelogenous leukemia HL60 cells.

Assessment of the frequency of additional cancers in patients with splenic marginal zone lymphoma.

Objectives: Solid second primary cancers (SPC) have become an issue of extensive research. The purpose of the present study was to estimate the standardised incidence ratio (SIR) and the absolute excess risk (AER) of SPC in patients with splenic marginal zone lymphoma (SMZL).

Methods: We investigated the incidence of additional cancers in 129 patients consecutively diagnosed with SMZL in three Italian haematological centres, asking the cooperating doctors for additional information on initial and subsequent therapies and on the onset and type of second cancers.

Deoxycoformycin (pentostatin) in the treatment of splenic marginal zone lymphoma (SMZL) with or without villous lymphocytes.

Background: Splenic marginal zone lymphoma (SMZL) is an infrequent B-cell neoplasm that pursues an indolent course. Signs and symptoms, mostly related to hypersplenism, are successfully managed by splenectomy. However, the therapy of patients who are not fit for a surgical procedure or who relapse after splenectomy, is still an unsettled issue.

Studies on the apoptotic activity of natural and synthetic retinoids: discovery of a new class of synthetic terphenyls that potently support cell growth and inhibit apoptosis in neuronal and HL-60 cells.

New terphenyl derivatives have been synthesized and tested for their effect on cell survival in serum-free cultures. These compounds protected HL60 cells from death and supported their growth with an activity higher than that of the natural 14-hydroxy-retro-retinol. Terphenyls 26 and 28 also possess antiapoptotic activity on neuronal cells, proving them as possible candidates for the treatment of neurodegenerative and ischemic diseases.

Pterostilbene and 3'-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells.

Pterostilbene and 3,5-hydroxypterostilbene are the natural 3,5-dimethoxy analogs of trans-resveratrol and piceatannol, two compounds which can induce apoptosis in tumor cells. In previous studies we demonstrated the importance of a 3,5-dimethoxy motif in conferring pro-apoptotic activity to stilbene based compounds so we now wanted to evaluate the ability of pterostilbene and 3,5-hydroxypterostilbene in inducing apoptosis in sensitive and resistant leukemia cells. When tested in sensitive cell lines, HL60 and HUT78, 3'-hydroxypterostilbene was 50-97 times more potent than trans-resveratrol in inducing apoptosis, while pterostilbene appeared barely active.

Hepatitis B virus reactivation and alemtuzumab therapy.

Reactivation of hepatitis B virus infection in subjects receiving cytotoxic treatment for heamatological malignancies occurs in 21-53% of chronic HBsAg carriers and in an unknown number of HBsAg negative subjects harbouring occult HBV infection. Immunotherapy with alemtuzumab, a humanized monoclonal antibody against CD52 epitopes on lymphocytes cells produces deep immunosuppression. We describe two subjects with chronic lymphocytic leukaemia and occult HBV infection who developed a virological and biochemical flare of hepatitis B following immunotherapy with alemtuzumab.

Heterocyclic and phenyl double-bond-locked combretastatin analogues possessing potent apoptosis-inducing activity in HL60 and in MDR cell lines.

Two new series of combretastatin (CA-4) analogues have been prepared. The alkenyl motif of CA-4 was replaced either by a five-membered heterocyclic (isoxazoline or isoxazole) or by a six-membered ring (pyridine or benzene). The new compounds have been evaluated for their effects on tubulin assembly and for cytotoxic and apoptotic activities.