Haematologica recent issues

Surgical treatment of a foscavir-resistant atypical Cytomegalovirus pneumonia in an allogeneic stem cell transplant recipient

2008-04-30

No association of the hypercoagulable state with sickle cell disease related pulmonary hypertension

2008-04-30

Early-onset haemochromatosis caused by a novel combination of TFR2 mutations(p.R396X/c.1538-2 A>G) in a woman of Italian descent

Gerolami, V., Le Gac, G., Mercier, L., Nezri, M., Berge-Lefranc, J-L., Ferec, C. — 2008-04-30

Reply to: Reduced intensity conditioning haematopoietic stem cell transplantation with mesenchymal stromal cells infusion for the treatment of metachromatic leukodystrophy: a case report. Haematologica 2008; 93:e11-13

Charnas, L., Eichler, F., Kohlschuetter, A., Tolar, J., Orchard, P.J. — 2008-04-30

Reduced intensity conditioning haematopoietic stem cell transplantation with mesenchymal stromal cells infusion for the treatment of metachromatic leukodystrophy: a case report

Meuleman, N., Tondreau, T., Vanhaelen, G., Lagneaux, L., Bron, D. — 2008-04-30

Secondary genomic alterations in non-Hodgkin's lymphomas: tumor-specific profiles with impact on clinical behavior

Bea, S., Campo, E. — 2008-04-30

Lymphoid neoplasms are associated with primary genetic alterations – mainly non-random reciprocal chromosomal translocations – and secondary alterations. In this perspective article, Drs. Bea and Campo discuss the importance of secondary chromosomal alterations in non-Hodgkin’s lymphomas. See related articles on pages 670, 680, and 688.

Molecular basis of thrombocytosis

Cazzola, M. — 2008-04-30

Thrombocytosis can be classified into three major categories: hereditary or familial thrombocytosis, thrombocytosis associated with myeloproliferative and/or myelodysplastic disorders (clonal thrombocytosis), and reactive (secondary) thrombocytosis. In this perspective article, Dr. Cazzola examines the molecular basis of familial thrombocytosis. See related article on page 706.

Interactions between genotype and phenotype in bleeding and thrombosis

Franchini, M., Mannucci, P. M. — 2008-04-30

The clinical phenotypic variability of disorders of blood coagulation is often the result of gene-gene, or gene-environment interactions. Drs. Franchini and Mannucci discuss this only partially understood subject. See related article on page 729.

Characterization of compound 584, an Abl kinase inhibitor with lasting effects

2008-04-30

Secondary resistance to imatinib is observed in patients with chronic myeloid leukemia. This study describes a novel Abl kinase inhibitor with long-lasting effects.

Effects of the aurora kinase inhibitors AZD1152-HQPA and ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts

Walsby, E., Walsh, V., Pepper, C., Burnett, A., Mills, K. — 2008-04-30

Aurora kinase inhibitors are being considered for treatment of acute myeloid leukemia. Findings of this study suggest that two such inhibitors are effective apoptosis-inducing agents in primary myeloid leukemia cells.

Comparative genome profiling across subtypes of low-grade B-cell lymphoma identifies type-specific and common aberrations that target genes with a role in B-cell neoplasia

2008-04-30

Low-grade B-cell lymphomas are very heterogeneous. This study of comparative genome profiling identifies type-specific aberrations that target genes with a role in B-cell lymphoid neoplasms. See related perspective article on page 641.

Genomic aberrations in mantle cell lymphoma detected by interphase fluorescence in situ hybridization. Incidence and clinicopathological correlations

2008-04-30

The primary genetic alteration of mantle cell lymphoma is a t(11;14)(q13;q32). Findings of this study provide novel insights into the pathogenesis of this lymphoid neoplasm, and in particular indicate that loss of chromosome 13q14 has additional prognostic relevance. See related perspective article on page 641.

Gain of chromosome region 18q21 including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma

2008-04-30

Diffuse large B-cell lymphoma is the most common lymphoma worldwide. Recent studies of gene expression profiling have identified subgroups of this lymphoid neoplasm with different prognosis. This study suggests that a gain of chromosome 18q21 including the MALT1 gene may involve an unfavorable prognosis. See related perspective article on page 641.

Selective influences in the expressed immunoglobulin heavy and light chain gene repertoire in hairy cell leukemia

2008-04-30

Hairy cell leukemia is a rare, chronic B-cell neoplasm characterized by leukemic hairy cells. This immunogenetic analysis of the expressed immunoglobulin heavy ad light chain gene repertoire suggests that immunoglobulin gene selection may play an important role in the pathognesis of this neoplasm.

A de novo splice donor mutation in the thrombopoietin gene causes hereditary thrombocythemia in a Polish family

2008-04-30

Familial thrombocytosis may be associated with gain-of-function mutations in the thrombopoietin (THPO) gene, or an activating germline mutation of MPL, the gene encoding thrombopoietin receptor. This study of a large family with thrombocytosis associated with a germline THPO mutations illustrates the hematologic and clinical features of this rare condition. See related article on page 646.

Simultaneous genotyping of coagulation factor XI type II and type III mutations by multiplex real-time polymerase chain reaction to determine their prevalence in healthy and factor XI-deficient Italians

2008-04-30

Factor XI deficiency is a rare autosomal recessive coagulopathy worldwide, although relatively common in Ashkenazi Jews. This study describes the presence of the F11 gene mutations in the Italian population and confirms their Jewish origin.

The Italian AICE-Genetics hemophilia A database: results and correlation with clinical phenotype

2008-04-30

This study reports a wide spectrum of factor 8 mutations in the large Italian database. Findings of the study indicate hat the type of mutations is a strong predictor of the clinical phenotype.

AB0 blood group and risk of venous or arterial thrombosis in carriers of factor V Leiden or prothrombin G20210A polymorphisms

2008-04-30

Several studies have shown an effect of AB0 blood group on hemostasis. Findings of this study indicate that non-00 group increases the risk and severity of venous thrombosis in carriers of prothrombotic polysmorphisms. See related perspective article on page 649.

Follow-up of healthy donors receiving granulocyte colony-stimulating factor for peripheral blood progenitor cell mobilization and collection. Results of the Spanish Donor Registry

2008-04-30

Information about the long-term follow-up and safety of granulocyte colony-stimulating factor administration to healthy donors is limited. Findings of this study indicate that clinical side effects are generally mild, and that development of secondary hematologic malignancy is unlikely.

Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders

2008-04-30

Three iron chelators are currently available for treatment of transfusion iron overload: deferoxamine, deferiprone, and deferasirox. This article reports the Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders.

Deficiency of heme-regulated eIF2{alpha} kinase decreases hepcidin expression and splenic iron in HFE-/- mice

Liu, S., Suragani, R. N.V.S., Han, A., Zhao, W., Andrews, N. C., Chen, J.-J. — 2008-04-30

Heme-regulated eIF2 balances heme and globin production by controlling globin synthesis. Its deficiency affects the phenotype of HFE^–/– mice by further decreasing hepcidin expression.

Sickle cell disease-related organ damage occurs irrespective of pain rate: implications for clinical practice

2008-04-30

This study shows that clinically relevant forms of organ damage occur irrespective of the frequency of painful crises in adults with sickle cell disease.

Anemia management in patients on peritoneal dialysis: efficacy and safety of epoetin {delta}

Spinowitz, B. S. — 2008-04-30

In this clinical trial, subcutaneously administered epoetin was effective and well tolerated for treatment of anemia in patients on peritoneal dialysis.

Phospho-CRKL monitoring for the assessment of BCR-ABL activity in imatinib-resistant chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia patients treated with nilotinib

2008-04-30

Findings of this study suggest that monitoring the actual BCR-ABL inhibition in nilotinib treated patients may be useful for establishing effective dosing and for detecting resistance against the drug.

Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-{alpha}: 5-year outcome

2008-04-30

This study confirms the excellent response to imatinib front-line therapy in patients with chronic myeloid leukemia. By contrast, most patients discontinued pegylated interferon- due to its side effects.

Cytoplasmic mutated nucleophosmin is stable in primary leukemic cells and in a xenotransplant model of NPMc+ acute myeloid leukemia in SCID mice

2008-04-30

Findings of this study indicate that NPM1 mutations are stable in patients with acute myeloid leukemia, providing a rationale for monitoring of minimal residual disease.

Clinical and demographic characteristics of Epstein-Barr virus-associated childhood Burkitt's lymphoma in Southeastern Brazil: epidemiological insights from an intermediate risk region

2008-04-30

This report describes clinical and demographic characteristics of Epstein-Barr virus-associated childhood Burkitt’s lymphoma in Southeastern Brazil.

A cross-sectional magnetic resonance imaging assessment of organ specific hemosiderosis in 180 thalassemia major patients in Hong Kong

2008-04-30

The Janus kinase 2 (JAK2) V617F mutation in Chinese patients with chronic myeloproliferative disorders

Xiao, Z., Zhang, Y., Li, L., Nie, L., Yang, L., Xu, S. — 2008-04-30

A prospective study of the separate predictive capabilities of 18[F]-FDG-PET and molecular response in patients with relapsed indolent non-Hodgkin's lymphoma following treatment with iodine-131-rituximab radio-immunotherapy

2008-04-30

Confirmation of the utility of the International Staging System and identification of a unique pattern of disease in Brazilian patients with multiple myeloma

2008-04-30

Serum-free light chain elevation is associated with a shorter time to treatment in Waldenstrom's macroglobulinemia

2008-04-30

No evidences for B-cell clonality by spectratyping analysis in patients with idiopathic thrombocytopenic purpura undergoing rituximab therapy

2008-04-30

A simple, novel and robust test to diagnose type I Glanzmann thrombasthenia

2008-04-30

A natural variant with a point mutation resulting in a homozygous Arg to His substitution at position 388 in prothrombin

2008-04-30

Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease

Johnson, C., Telen, M. J. — 2008-03-31

The vaso-occlusive process in sickle cell disease is responsible for much of the morbidity and mortality observed in this condition, and adhesion molecules play a crucial role in it. Hydroxyurea treatment has proven clinical benefit in sickle cell disease, and Drs. Johnson and Telen discuss how this drug may affect the adhesive interactions between blood cells and the endothelium leading to vaso-occlusion. See related article on page 502.

Fanconi anemia is a highly penetrant cancer susceptibility syndrome

Dokal, I. — 2008-03-31

Over the last 20 years, major advances have been made in our understanding of the biology of Fanconi anemia, which now represents one of the best-defined inherited bone marrow failure syndromes. In this perspective article, Dr. Dokal analyzes the factors predisposing to malignancy in Fanconi anemia. See related article on page 511.

The epidemiology of acquired aplastic anemia

Young, N. S., Kaufman, D. W. — 2008-03-31

Our understanding of the epidemiology of aplastic anemia has improved considerably based on several decades of laboratory and clinical research. Drs. Young and Kaufman summarize our current knowledge and discuss clinical implications of epidemiological studies. See related article on page 518.

Signaling pathways involved in the development of T-cell acute lymphoblastic leukemia

Staal, F. J.T., Langerak, A. W. — 2008-03-31

T-cell acute lymphoblastic leukemia results from the malignant transformation of normal developing T cells in the thymus, the so-called thymocytes. Drs. Staal and Langerak analyze the signaling pathways involved in the pathophysiology of this disorder. See related articles on page 524 and 533.

Protein S deficiency

D'Angelo, A., Vigano D'Angelo, S. — 2008-03-31

An association of familial protein S deficiency with increased venous thromboembolic risk was first reported in 1984. In this perspective article, Drs. D’Angelo and Viganò D’Angelo summarize our current understanding of the pathophysiology of protein S deficiency. See related article on page 574.

Modulation of erythroid adhesion receptor expression by hydroxyurea in children with sickle cell disease

2008-03-31

Hydroxyurea is currently employed for prevention of vaso-occlusive events in patients with sickle cell disease, but its mechanism of action is largely unknown. Findings of this study suggest that hydroxyurea acts during erythroid development by modulating adhesion receptor expression. See related perspective article on page 481.

Cancer risks in Fanconi anemia: findings from the German Fanconi Anemia Registry

Rosenberg, P. S., Alter, B. P., Ebell, W. — 2008-03-31

Fanconi anemia is an inherited genomic instability syndrome associated with progressive bone marrow failure and a high risk of acute myeloid leukemia and solid tumors. This study confirms this high risk, the estimated ratio of observed to expected malignancies being 868 for acute myeloid leukemia and 26 for all solid tumors. See related perspective article on page 486.

Epidemiology of aplastic anemia: a prospective multicenter study

2008-03-31

Aplastic anemia is a rare disease whose incidence varies considerably worldwide. In this study conducted in the metropolitan area of Barcelona, the overall incidence was 2.34 per million inhabitants per year. The survival rate at 2 years was 57%, confirming the severity of this condition. See related perspective article on page 489.

Bone marrow stromal cells and the upregulation of interleukin-8 production in human T-cell acute lymphoblastic leukemia through the CXCL12/CXCR4 axis and the NF-{kappa}B and JNK/AP-1 pathways

2008-03-31

Cytokines released in the bone marrow likely play an important role in the growth of T-cell acute lymphoblastic leukemia. Findings of this study suggest that CXCL12 (also known as SDF-1) can regulate interleukin-8 production in leukemic T cells. See related perspective article on page 493.

In vitro validation of {gamma}-secretase inhibitors alone or in combination with other anti-cancer drugs for the treatment of T-cell acute lymphoblastic leukemia

2008-03-31

Activating NOTCH-1 mutations are common in T-cell acute lymphoblastic leukemia. Inhibition of NOTCH-1 signaling by -secretase inhibitors causes cell cycle block. Findings of this study suggest that prolonged treatment with -secretase inhibitors and combinations with other drugs are required to obtain visible effects on T-cell acute lymphoblastic leukemia cells lines. See related perspective article on page 493.

Detection of somatic quantitative genetic alterations by multiplex polymerase chain reaction for the prediction of outcome in diffuse large B-cell lymphomas

2008-03-31

Genomic gains and losses play a crucial role in the development of diffuse large B-cell lymphoma. This study shows that multiplex polymerase chain reaction of short fluorescent fragments is a reliable method for detecting somatic quantitative genetic alterations in diffuse large B-cell lymphoma.

Minimal residual disease detection in mantle cell lymphoma: methods and significance of four-color flow cytometry compared to consensus IGH-polymerase chain reaction at initial staging and for follow-up examinations

2008-03-31

Multicolor flow cytometry is increasingly employed in the diagnosis and follow-up of mantle cell lymphoma. Findings of this study indicate that multicolor flow cytometry is a very valuable method for accurate initial staging of mantle cell lymphoma.

Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression

2008-03-31

Novel therapeutic agents have become available for patients with multiple myeloma in the last few years. This study conducted by the Spanish PETHEMA and GEM groups investigated the effect of bortezomib plus melphalan and prednisone in elderly patients with newly diagnosed multiple myeloma. Treatment was highly active and well tolerated, with 85% of patients alive at 3 years.

The effect of platelet activation on the hypercoagulability induced by murine monoclonal antiphospholipid antibodies

2008-03-31

Antiphospholipid antibodies are associated with an increased risk of thrombosis. Findings of this study suggest that platelet activation reinforces the hypercoagulability induced by interference of antiphospholipid antibodies/target complexes with coagulation reactions on membrane surfaces.

Functional characterization of twelve natural PROS1 mutations associated with anticoagulant protein S deficiency

2008-03-31

The molecular mechanisms by which PROS1 mutations result in protein S deficiency are still unknown for many mutations. Findings of this study indicate that the main mechanism for the deficiency associated with mutations that generate a premature termination codon is not the synthesis of a truncated protein, but the exclusion of the mutated allele.

A prospective analysis of the genotypic diversity and dynamics of the Candida albicans colonizing flora in neutropenic patients with de novo acute leukemia

2008-03-31

This study was aimed at investigating the dynamics and heterogeneity of C. albicans flora in patients with de novo acute leukemia. Its findings suggest that genetic evolution of the colonizing C. albicans flora is uncommon in patients with acute leukemia.

Quality of life of female caregivers of children with sickle cell disease: a survey

2008-03-31

This Dutch survey demonstrates a lower quality of life in female caregivers of children with sickle cell disease than in the healthy female population and caregivers of healthy children with the same socioeconomic status. Therefore, better support is needed to improve the quality of life of both children with sickle cell disease and their caregivers.

Improvements in survival of adults diagnosed with acute myeloblastic leukemia in the early 21st century

Pulte, D., Gondos, A., Brenner, H. — 2008-03-31

This study shows that 5- and 10-year relative survival has improved substantially for younger patients with acute myeloid leukemia over the last 25 years. By contrast, survival remains poor in the oldest age group, which include a large proportion of patients with acute myeloid leukemia.

Differential role of CD97 in interleukin-8-induced and granulocyte-colony stimulating factor-induced hematopoietic stem and progenitor cell mobilization

van Pel, M., Hagoort, H., Kwakkenbos, M. J., Hamann, J., Fibbe, W. E. — 2008-03-31

CD97 is a transmembrane receptor involved in neutrophil migration. This study shows that CD97 plays a role in interleukin-8-induced hematopoietic stem cell and progenitor mobilization.

Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation

Canalli, A. A., Franco-Penteado, C. F., Saad, S. T.O., Conran, N., Costa, F. F. — 2008-03-31

Adhesive interactions between blood cells and endothelium lead to vaso-occlusion in sickle cell disease. This study suggests that pharmacological nitric oxide donation may reduce neutrophil adhesion to vascular endothelium.

Peptide-nucleic acid-mediated enriched polymerase chain reaction as a key point for non-invasive prenatal diagnosis of {beta}-thalassemia

2008-03-31

This study describes a novel approach to non-invasive pre-natal diagnosis of β-thalassemia based on microchip analysis of fetal DNA extracted from maternal plasma.

Neurodegenerative central nervous system disease as late sequelae of Langerhans cell histiocytosis. Report from the Japan LCH Study Group

2008-03-31

Langerhans’ cell histiocytosis can affect the central nervous system, where it frequently manifests as diabetes insipidus. Cerebellar ataxia and other neurological defects can represent late sequelae of this disorder.

Hepatocyte growth factor promotes migration of human myeloma cells

2008-03-31

This study demonstrates that myeloma cells can be attracted to hepatocyte growth factor in concentrations known to be present in the bone marrow of patients with multiple myeloma.

Primary extramedullary plasmacytoma: similarities with and differences from multiple myeloma revealed by interphase cytogenetics

2008-03-31

Primary extramedullary plasmacytoma and multiple myeloma show similar chromosomal alterations, as detected by fluorescence in situ hybridization.

Accurate Rh phenotype determination by reticulocyte mRNA typing shortly after multiple transfusions

2008-03-31

This study describes a method for correctly typing patients’ own Rh-antigens after multiple transfusions.

Single nucleotide polymorphism microarray analysis of karyotypically normal acute myeloid leukemia reveals frequent copy number neutral loss of heterozygosity

Tyybakinoja, A., Elonen, E., Vauhkonen, H., Saarela, J., Knuutila, S. — 2008-03-31

Relapse and death during first remission in acute myeloid leukemia

2008-03-31

Endothelial cell activation by immunoglobulins from patients with immune thrombocytopenic purpura or with antiphospholipid syndrome

2008-03-31

Role of polymorphisms of CC-chemokine receptor-5 gene in acute myocardial infarction and biological implications for longevity

2008-03-31

Breakthrough C. parapsilosis and C. guilliermondii blood stream infections in allogeneic hematopoietic stem cell transplant recipients receiving long-term caspofungin therapy

2008-03-31

Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis

2008-02-29

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.

Transient global amnesia associated with the infusion of DMSO-cryopreserved autologous peripheral blood stem cells

2008-02-29

Dimethylsulfoxide (DMSO) is a solvent commonly used for the cryopreservation of autologous peripheral blood stem cells (APBSC). Side effects upon infusion of DMSO-cryopreserved APBSC mainly consist of nausea, emesis, chills, rigors, and cardiovascular events, such as bradyarrhythmia or hypotension. We report the case of a patient who received DMSO-cryopreserved APBSC after myeloablative chemotherapy for a relapsing lymphoma. The patient developed a rare reaction during the infusion manifesting as transient global amnesia. The clinical course during the reaction is described and an explanation of the possible causes is discussed. This observation underlines the need for an adequate DMSO depletion to limit neurotoxicity or other adverse manifestations.

TGF-beta 1 and urinary excretion of pyridinium crosslinks: two often overlooked risk factors for assessing risk of progression in patients with monoclonal gammopathy of undetermined significance

Kapoor, S. — 2008-02-29

Hematopoietic stem cell mobilization

Lemoli, R. M., D'Addio, A. — 2008-02-29

There are advantages from reinfusing autologous mobilized peripheral blood stem cells rather than bone marrow hematopoietic stem cells. This article focuses on the bio-molecular mechanisms underlying the release of hematopoietic stem cells from the bone marrow to help the understanding of novel strategies to make stem cell collection more effective. See related article on page 347.

Towards the genetic treatment of {beta}-thalassemia: new disease models, new vectors, new cells

Moi, P., Sadelain, M. — 2008-02-29

The transfer of a regulated globin gene in autologous hematopoietic stem cells is an attractive therapeutic approach to β-thalassemia, since, in principle, it is applicable to all patients. This commentary reviews recent advances in animal models, globin vector design and stem cell isolation. See related article on page 356.

Prevention of thrombosis in polycythemia vera and essential thrombocythemia

Landolfi, R., Di Gennaro, L. — 2008-02-29

Thrombotic events are a dominant clinical feature of polycythemia vera and essential thrombocythemia. Estimating the vascular risk and choosing the best antithrombotic strategy are crucial issues in the management of these disorders. This article reviews the most important risk factors for thrombosis and focuses on the available therapeutic strategies for reducing the vascular risk. See related article on page 372.

Secondary malignancies after therapy of indolent non-Hodgkin's lymphoma

Friedberg, J. W. — 2008-02-29

Over the past decade the survival of patients with indolent non-Hodgkin’s lymphoma has improved significantly. As a consequence, patients have more time to develop secondary effects of chemotherapy and radiation therapy. This perspective article focuses on risks and risk factors for the development of solid tumors in patients with such lymphomas. See related article on page 398.

Multipotent mesenchymal stromal cells from amniotic fluid: solid perspectives for clinical application

2008-02-29

Mesenchymal stromal cells are multipotent cells potentially useful in regenerative medicine. These cells are usually obtained from the bone marrow; however, the cell dose may be a critical factor, and alternative sources need to be explored. This study suggests that amniotic fluid represents a rich source of mesenchymal stromal cells.

Pegylated granulocyte colony-stimulating factor mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor

2008-02-29

Stem cells can be mobilized into the peripheral blood using cytokines, cytotoxic chemotherapy or a combination of both. Stimulation with pegylatedgranulocyte colony-stimulating factor or granulocyte colony-stimulating factor results in different expression of key regulatory genes and different functional properties of mobilized hematopoietic stem and progenitor cells.

A novel transgenic mouse model produced from lentiviral germline integration for the study of {beta}-thalassemia gene therapy

2008-02-29

Lentiviral-mediated gene therapy has been successfully applied in the treatment of β-thalassemia. In this study transgenic mice with stable expression of a lentivirus carrying the human β-globin gene were obtained. These animals provide a useful model to investigate the stable effect of gene therapy in β-thalassemia.

SBDS-deficient cells undergo accelerated apoptosis through the Fas-pathway

2008-02-29

Ninety percent of patients with Shwachman-Diamond syndrome, an inherited bone marrow dysfunction, have mutations in the Shwachman-Bodian-Diamond syndrome gene (SBDS). However, the relationship between SBDS and cell survival is unknown. This study shows that inhibition of SBDS results in accelerated apoptosis and investigates the mechanisms involved in this process.

Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments

2008-02-29

Polycythemia vera and essential thrombocythemia are typically complicated by thrombosis. According to this multicenter study recurrent thrombosis is observed in about one third of patients. Cytoreduction protects against recurrence of thrombosis. The contemporary use of oral anticoagulants or antiplatelet agents further reduce the incidence of re-thrombosis.

Activation of cytotoxic T-cell receptor {gamma}{delta} T lymphocytes in response to specific stimulation in myelodysplastic syndromes

2008-02-29

Several immune defects have been shown to be present in patients with myelodysplastic syndromes. This study suggests that there are immune surveillance defects, which may contribute to the pathogenesis of these syndromes. Cytotoxic T-cell receptor T lymphocytes can be expanded in a high proportion of patients, which may be of particular value in the development of immunotherapy.

Evaluation of response to fractionated radioimmunotherapy with 90Y-epratuzumab in non-Hodgkin's lymphoma by 18F-fluorodeoxyglucose positron emission tomography

2008-02-29

FDG-PET imaging has been proven to be more accurate than conventional imaging for assessment of lymphoma response to therapy. This study evaluates the usefulness of FDG-PET for predicting response to radioimmunotherapy in patients with refractory lymphoma. The results suggest that positive FDG-PET findings 6 weeks after radioimmunotherapy predict significantly earlier relapse.

Secondary malignancies after treatment for indolent non-Hodgkin's lymphoma: a 16-year follow-up study

2008-02-29

There is relatively little information on secondary cancers after non-Hodgkin’s lymphomas. This long-term follow-up study determines the incidence rate and identifies subgroups of non-Hodgkin's lymphoma patients with increased incidences of secondary malignancy.

A phase 2 pilot study of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin's lymphoma receiving chemotherapy

2008-02-29

This phase 2 randomized, double-blind trial examines the efficacy of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitors cells following chemotherapy in patients with non-Hodgkin’s lymphoma. The results of the study suggest that pegfilgrastim may provide a suitable alternative to filgrastim in this setting.

Clonal heterogeneity in chronic lymphocytic leukemia cells: superior response to surface IgM cross-linking in CD38, ZAP-70-positive cells

2008-02-29

The reasons why immunoglobulin gene mutation status and expression of ZAP-70 and CD38 influence disease progression in chronic lymphocytic leukemia are still undefined. This study shows that CD38⁺, ZAP-70⁺ cells have a greater capacity for signalling through the B-cell receptor and suggests a function for B-cell receptor signaling in promoting cell expansion.

CD4+CD25+FOXP3+ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation

2008-02-29

Peripheral tolerance is largely maintained by immunosuppressive regulatory T cells, which typically co-express CD4, CD25 and FOXP3. This study analyzes lymphocyte subsets in myeloma patients treated with allogeneic stem cell transplantation, and shows that donor-derived regulatory T cells expand faster than conventional CD4⁺ T cells and have a strong inhibitory function.

Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders

2008-02-29

In multiple myeloma, the use of multiparametric flow cytometry in many laboratories is currently restricted to clinical research studies and the differential diagnosis of unusual cases. This article report the indications of the European Myeloma Network for flow cytometry in patients with monoclonal gammopathies, and the technical recommendations for the analysis of plasma cells.

NPM1 mutations and cytoplasmic nucleophosmin are mutually exclusive of recurrent genetic abnormalities: a comparative analysis of 2562 patients with acute myeloid leukemia

2008-02-29

NPM1 mutations, causing aberrant cytoplasmic expression of nucleophosmin, are the most frequent genetic alteration in acute myeloid leukemia with a normal karyotype. This study confirms in a large series of patients that NPM1 mutations and cytoplasmic nucleophosmin are mutually exclusive of recurrent genetic abnormalities.

Histone deacetylase inhibitor treatment downregulates VLA-4 adhesion in hematopoietic stem cells and acute myeloid leukemia blast cells

Mahlknecht, U., Schonbein, C. — 2008-02-29

The migration of hematopoietic progenitor cells depends on a number of cell surface molecules. This study shows that treatment with histone deacetylase inhibitors downregulates the integrin VLA-4 on acute myeloid leukemia blast cells and hematopoietic stem cells, resulting in decreased adhesion of these cells to mesenchymal stromal cells.

Autoimmune thrombocytopenia in non-Hodgkin's lymphomas

2008-02-29

Autoimmune thrombocytopenia is a potentially life-threatening complication in non-Hodgkin’s lymphomas. This study focuses on the temporal relationship between autoimmune thrombocytopenia and lymphoma, the frequency in lymphoma subtypes, laboratory data and treatment outcome.