Haematologica recent issues

Factor XI mutation and the origin of Ashkenazi Jews

Zoossmann-Diskin, A. — 2008-09-30

Reply to: [Factor XI mutation and the origin of Ashkenazi Jews. Haematologica 2008; 93:e59]

2008-09-30

Efficacy of cyclosporine as a single agent therapy in chronic idiopathic thrombocytopenic purpura

Choudhary, D.R., Naithani, R., Mahapatra, M., Kumar, R., Mishra, P., Saxena, R. — 2008-09-30

Reply to: [Efficacy of cyclosporine as a single agent therapy in chronic idiopathic thrombocytopenic purpura". Haematologica 2008; 93:e61]

Emilia, G., Luppi, M., Morselli, M., Forghieri, F., Potenza, L., Torelli, G. — 2008-09-30

Reply to: [Non-Hodgkin's lymphoma and residential proximity to toxic industrial waste in Southern Israel. Haematologica 2005; 90:1709-10]

Carel, R.S. — 2008-09-30

New and old players in the hepcidin pathway

Camaschella, C., Silvestri, L. — 2008-09-30

The identification of the liver peptide hepcidin at the beginning of the new millennium opened a new era in our understanding of iron metabolism. In this perspective article, Dr. Camaschella and Silvestri summarize current knowledge of the hepcidin pathway and of the regulation of the hepcidin expression. In particular, they discuss the function of matriptase-2, a transmembrane serine protease that is encoded by the TMPRSS6 gene and suppresses hepcidin production. See related paper on pages 1466, 1473 and 1550.

Novel thrombopoietic agents: a new era for management of patients with thrombocytopenia

George, J. N., Terrell, D. R. — 2008-09-30

After many decades of an orphan existence, immune thrombocytopenic purpura is a central focus for the clinical development of multiple, novel thrombopoietic agents. In this perspective article, Drs. George and Terrell describe the molecular spectrum of thrombopoietic agents that are currently under development. See related paper on page 1495.

Allogeneic hematopoietic stem cell transplantation for myelofibrosis

Rondelli, D. — 2008-09-30

Primary myelofibrosis or myelofibrosis secondary to polycythemia vera or essential thrombocythemia can be cured only by means of allogeneic hematopoietic stem cell transplantation at present. In this perspective article, Dr. Rondelli discusses which patients are the best candidates for transplantation, and the optimal transplantation procedures. See related paper on page 1514.

Adoptive T-cell therapy for malignant disorders

Powell, D. J., Levine, B. L. — 2008-09-30

Adoptive cell transfer using ex vivo manipulated T lymphocytes has emerged as an important advance in cancer immunotherapy, allowing for re-education and re-setting of the host immune system. In this perspective article, Drs. Powell and Levine discuss the current situation in this field. See related paper on page 1523.

Factors that influence short-term homing of human bone marrow-derived mesenchymal stem cells in a xenogeneic animal model

Kyriakou, C., Rabin, N., Pizzey, A., Nathwani, A., Yong, K. — 2008-09-30

Human mesenchymal stem cells are potential agents for tissue regeneration, enhancing hematopoietic stem cell transplantation and delivering genes of therapeutic interest. This study shows that tissue homing of systemically administered mesenchymal stem cells can be increased by enforced expression of CXCR4, at least in irradiated hosts.

Hemojuvelin N-terminal mutants reach the plasma membrane but do not activate the hepcidin response

Pagani, A., Silvestri, L., Nai, A., Camaschella, C. — 2008-09-30

Hemojuvelin positively modulates the iron regulator hepcidin. Mutations of the gene encoding for hemojuvelin cause juvenile hemochromatosis, characterized by hepcidin deficiency and severe iron overload. This study shows that the delayed export and retention in the endoplasmic reticulum of some N-terminal mutants could contribute to the pathogenesis of juvenile hemochromatosis. See related perspective article on page 1441.

A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron

2008-09-30

Previous studies have described a familial syndrome characterized by iron malabsorption, hypoferremia, and microcytic anemia that did not respond to oral iron and responded only partly to parenteral iron. In this work, Melis and coworkers studied a Sardinian family with this inherited condition. They found a homozygous causal mutation in the TMPRSS6 gene in affected members, who had inappropriately elevated levels of serum and urinary hepcidin. See related perspective article on page 1441.

Accumulation of hypoxia-inducible factor-1{alpha} protein and its role in the differentiation of myeloid leukemic cells induced by all-trans retinoic acid

Zhang, J., Song, L.-P., Huang, Y., Zhao, Q., Zhao, K.-W., Chen, G.-Q. — 2008-09-30

That hypoxia-inducible factor-1 (HIF-1) contributes to the differentiation of acute myeloid leukemia cells via transcriptional activity-independent mechanisms. This study shows that increased HIF-1 levels contribute to all-trans retinoic acid-induced differentiation of acute myeloid leukemia cells cells.

Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study

2008-09-30

The effects of L-asparaginase on hemostasis during induction chemotherapy of acute lymphoblastic leukemia of lymphoblastic lymphoma are less defined in adults than in children. This retrospective study suggests that antithrombin concentrates may have a beneficial effect on the outcome of adults treated for acute lymphoblastic leukemia with L-asparaginase.

The effect of a novel, small non-peptidyl molecule butyzamide on human thrombopoietin receptor and megakaryopoiesis

2008-09-30

Thrombocytopenia is found in several conditions, and in many of them no treatment is available apart from platelet transfusion. Findings of this study suggest that butyzamide, an orally bioavailable human Mpl activator, may increase platelet production. See related perspective article on page 1445.

Molecular characterization of three novel splicing mutations causing factor V deficiency and analysis of the F5 gene splicing pattern

2008-09-30

Factor V deficiency is a rare autosomal recessive hemorrhagic disorder, associated with bleeding manifestations of variable severity. This paper reports the functional consequences of three novel splicing mutations leading to FV deficiency.

Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

2008-09-30

In this GITMO study, Patriarca and coworkers evaluated the outcome of patients with myelofibrosis who underwent allogeneic stem cell transplantation, and the impact of prognostic factors. They conclude that the outcome of myelofibrosis patients who underwent allogeneic stem cell transplantation significantly improved after 1996 due to the reduction in transplant-related mortality. See related perspective article on page 1449.

The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the induction of ex vivo expansion of functional human antitumor T cells

2008-09-30

The aim of this study was to engineer an artificial APC-based system with the properties of a fluid cellular membrane and the flexibility derived from an artificial structure that could be tailored to carry the desired immunostimulatory molecules. The authors conclude that their artificial antigen-presenting cells might represent an efficient tool to rapidly obtain a sufficient number of functional T cells for adoptive immunotherapy in patients with cancer. See related perspective article on page 1452.

Genetic engineering of virus-specific T cells with T-cell receptors recognizing minor histocompatibility antigens for clinical application

2008-09-30

Donor lymphocyte infusion is an effective form of adoptive immunotherapy for hematologic malignancies after allogeneic stem cell transplantation, but is frequently associated with development of graft-versus-host disease. This study describes an efficient method for generating T-cell receptors-engineered virus-specific T cells, which may provide effective adoptive anti-tumor therapy after allogeneic stem cell transplantation, with a low risk of graft-versus-host disease.

Recent trends in long-term survival of patients with chronic myelocytic leukemia: disclosing the impact of advances in therapy on the population level

Brenner, H., Gondos, A., Pulte, D. — 2008-09-30

This analysis discloses a dramatic recent increase in long-term survival of younger patients with chronic myeloid leukemia, which most likely reflects rapid dissemination of advances in therapy on the population level.

Serum hepcidin level and erythropoietic activity after hematopoietic stem cell transplantation

2008-09-30

In this study, an inverse relationship between erythroid activity and serum hepcidin was found after hematopoietic stem cell transplantation.

Long-term responses and outcomes following immunosuppressive therapy in large granular lymphocyte leukemia-associated pure red cell aplasia: a Nationwide Cohort Study in Japan for the PRCA Collaborative Study Group

2008-09-30

This report describes long-term responses following immunosuppressive therapy in large granular lymphocyte leukemia-associated pure red cell aplasia.

Rapid identification of JAK2 exon 12 mutations using high resolution melting analysis

Jones, A. V., Cross, N. C.P., White, H. E., Green, A. R., Scott, L. M. — 2008-09-30

In this study, high resolution melting analysis was found to be a rapid, sensitive and high-throughput technique for screening for JAK2 exon 12 mutations.

Nucleophosmin mutation in Southeast Asian acute myeloid leukemia: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations

Boonthimat, C., Thongnoppakhun, W., Auewarakul, C. U. — 2008-09-30

This report shows that NPM1 mutations were most prevalent in Thai patients with acute myeloid leukemia with normal karyotype.

Impaired dexamethasone-related increase of anticoagulants is associated with the development of osteonecrosis in childhood acute lymphoblastic leukemia

te Winkel, M. L., Appel, I. M., Pieters, R., van den Heuvel-Eibrink, M. M. — 2008-09-30

In childhood acute lymphoblastic leukemia, a hypercoagulable state may result from a lower dexamethasone-related increase of antithrombin and protein S and the subsequent decline of these anticoagulants below normal levels after introduction of asparaginase.

CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemia

2008-09-30

Findings of this study suggest that CD49d expression may be useful for the initial prognostic assessment of patients with chronic lymphocytic leukemia in the initial stage.

The transcription factor nuclear factor Y regulates the proliferation of myeloid progenitor cells

2008-09-30

Congenital sideroblastic anemia associated with germline polymorphisms reducing expression of FECH

Caudill, J. S., Imran, H., Porcher, J. C., Steensma, D. P. — 2008-09-30

Correlation of liver iron concentration determined by R2 magnetic resonance imaging with serum ferritin in patients with thalassemia intermedia

Taher, A., El Rassi, F., Isma'eel, H., Koussa, S., Inati, A., Cappellini, M. D. — 2008-09-30

Pregnancy outcome in patients with {beta}-thalassemia intermedia at two tertiary care centers, in Beirut and Milan

2008-09-30

Continuous improvement of bone mineral density two years post zoledronic acid discontinuation in patients with thalassemia-induced osteoporosis: long-term follow-up of a randomized, placebo-controlled trial

2008-09-30

Large deletion in UGT1A1 gene encompassing the promoter and the exon 1 responsible for Crigler-Najjar type I syndrome

Petit, F. M., Hebert, M., Gajdos, V., Capel, L., M'Rad, R., Labrune, P. — 2008-09-30

Two novel variants of MOZ-CBP fusion transcripts in spontaneously remitted infant leukemia with t(1;16;8)(p13;p13;p11), a new variant of t(8;16)(p11;p13)

Terui, K., Sato, T., Sasaki, S., Kudo, K., Kamio, T., Ito, E. — 2008-09-30

Pulmonary extramedullary hematopoiesis in patients with myelofibrosis undergoing allogeneic stem cell transplantation

Chunduri, S., Gaitonde, S., Ciurea, S. O., Hoffman, R., Rondelli, D. — 2008-09-30

Exon 8 splice site mutations in the gene encoding the E3-ligase CBL are associated with core binding factor acute myeloid leukemias

Abbas, S., Rotmans, G., Lowenberg, B., Valk, P. J.M. — 2008-09-30

Genetic variation in genes expressed in the germinal center and risk of B cell lymphoma among Caucasians

Scott, K., Adamson, P. J., Willett, E. V., Worrillow, L. J., Allan, J. M. — 2008-09-30

Variability and heritability of hemoglobin concentration: an opportunity to improve understanding of anemia in older adults

Patel, K. V. — 2008-08-29

Hemoglobin concentration varies substantially in humans. In this perspective article, Dr. Patel examines the many factors responsible for this variability, including genetic ones. The large interindividual variation in hemoglobin concentration has important implications for the diagnosis and treatment of anemia, particularly in older adults. See related paper on page 1372.

Genotype/phenotype correlation in hereditary spherocytosis

Iolascon, A., Avvisati, R. A. — 2008-08-29

Hereditary spherocytosis is found worldwide and has a prevalence of about 1 in 2000. This inherited hemolytic disease is caused by germline mutations in genes encoding proteins of the red cell membrane. In this perspective article, Drs. Iolascon and Avvisati examine genotype/phenotype relationships, and discuss their clinical implications. See related paper on page 1310.

Apoptotic pathways to death in myelodysplastic syndromes

Fontenay, M., Gyan, E. — 2008-08-29

The pathophysiology of myelodysplastic syndromes is largely unknown. In this perspective article, Drs. Fontenay and Gyan examine physiological cell death. They then discuss the dysregulated apoptotic pathways to death in myelodysplastic syndromes, and the usefulness of animal models for improving our understanding of this dysregulation. See related paper on page 1394.

The pathogenesis of classical Hodgkin's lymphoma: what can we learn from analyses of genomic alterations in Hodgkin and Reed-Sternberg cells?

Janz, M., Mathas, S. — 2008-08-29

Classical Hodgkin’s lymphoma is one of the most common malignant lymphomas. In the vast majority of cases it is curable at the early stages, but the treatment of advanced disease stages or refractory patients is challenging. In this perspective article, Drs. Janz and Mathas discuss the pathogenesis of classical Hodgkin’s lymphoma and examine the numerous genetic defects identified so far. They conclude that the challenge for future work will be to identify the unifying molecular defects responsible for this malignancy. See related paper on page 1318.

Allogeneic transplantation in multiple myeloma

Gahrton, G., Bjorkstrand, B. — 2008-08-29

Allogeneic stem cell transplantation from an HLA-identical sibling has proven to be useful in patients with multiple myeloma, possibly also because of a graft-versus-myeloma effect. In this perspective article, Drs. Gahrton and Björkstrand examine the results obtained so far, and discuss potential strategies to improve the outcome of patients with multiple myeloma undergoing this therapeutic procedure. See related paper on page 1343.

The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes

2008-08-29

Mesenchymal stem cells are multipotent non-hematopoietic progenitor cells capable of differentiating into various lineages including osteoblasts, chondrocytes and adipocytes. The findings of this study indicate that mesenchymal stem cells promote survival and inhibit proliferation and maturation of B cells, and support a role of these cells in the immune response.

Clinical and hematologic features of 300 patients affected by hereditary spherocytosis grouped according to the type of the membrane protein defect

2008-08-29

The molecular basis of hereditary spherocytosis is highly heterogeneous, involving the genes encoding for spectrin, ankyrin, band 3 and protein 4.2. The findings of this retrospective study show that splenectomy corrected anemia in patients with all molecular subtypes of hereditary spherocytosis. Thus, the definition of the red cell membrane defect in hereditary spherocytosis has no major clinical implications, but may be useful for a differential diagnosis from other hematologic disorders that mimic this hemolytic anemia. See related perspective article on page 1283.

Detection of genomic imbalances in microdissected Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma by array-based comparative genomic hybridization

2008-08-29

Cytogenetic analysis of classical Hodgkin’s lymphoma is limited by the low content of the neoplastic Reed-Sternberg cells in the affected tissues. The present study demonstrates that array comparative genomic hybridization of microdissected Hodgkin-Reed-Sternberg cells is suitable for identifying and characterizing chromosomal imbalances. Se related perspective article on page 1292.

Chromosomal alterations detected by comparative genomic hybridization in subgroups of gene expression-defined Burkitt's lymphoma

2008-08-29

This study of the Leukemia and Lymphoma Molecular Profiling Project (LLMPP) shows that pediatric and adult Burkitt’s lymphoma are molecularly homogeneous, whereas ‘discrepant Burkitt’s lymphoma’ differs in underlying genetic and clinical features from typical/atypical Burkitt’s lymphoma.

Second malignancies after treatment of diffuse large B-cell non-Hodgkin's lymphoma: a GISL cohort study

2008-08-29

Improved treatment has increased the life expectancy of patients with non-Hodgkin’s lymphoma, but the risk of second cancer in patients treated for diffuse large B-cell lymphoma is unclear. This Italian study shows that only young patients have an increased incidence ratio of second malignancies, while the incidence ratio in patients aged over 59 years matched that in the Italian general population.

Clinical impact of human Jurkat T-cell-line-derived antithymocyte globulin in multiple myeloma patients undergoing allogeneic stem cell transplantation

2008-08-29

Antithymocyte globulin is used in allogeneic stem cell transplantation to induce in vivo T-cell depletion to facilitate engraftment and lower graft-versus-host disease. Antithymocyte globulin also has anti-myeloma activity in vitro. This study shows that inclusion of antithymocyte globulin in allogeneic stem cell transplantation protocols for patients with multiple myeloma may increase remission rates. See related perspective article on page 1295.

Thrombomodulin-modified thrombin generation after in vivo recombinant factor VIII treatment in severe hemophilia A

2008-08-29

Thrombin generation has been shown to reflect coagulation potential and factor VIII (FVIII) levels in patients with hemophilia A. This study shows that thrombin generation in the presence of thrombomodulin reflects plasma FVIII levels better.

Endothelial protein C receptor polymorphisms and risk of myocardial infarction

2008-08-29

Haplotypes A1 and A3 in the endothelial protein C receptor gene are tagged by the 4678G/C and 4600A/G polymorphisms, respectively, and have been reported to influence the risk of venous thromboembolism. This study shows that A1 and A3 haplotype carriers have a reduced risk of myocardial infarction.

Practice guidelines for the management of extranodal non-Hodgkin's lymphomas of adult non-immunodeficient patients. Part I: primary lung and mediastinal lymphomas. A project of the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation

2008-08-29

Extranodal non-Hodgkin’s lymphomas constitute 20–25% of all cases of non-Hodgkin’s lymphomas and can be managed with very different therapeutic strategies. This article summarizes ad hoc guidelines for the management of this disease.

Variation of hemoglobin levels in normal Italian populations from genetic isolates

2008-08-29

This study provides a dataset of hemoglobin levels for normal subjects of different geographical origin and indicates that hemoglobin levels are substantially influenced by heritable components. See related perspective article on page 1281.

Chronic preclinical safety evaluation of HematideTM, a pegylated peptidic erythropoiesis stimulating agent in monkeys

2008-08-29

Hematide is a synthetic peptide-based, pegylated erythropoiesis stimulating agent in clinical development for treatment of anemia. In this study, hematide administration was associated with time and dose-dependent polycythemia in monkeys.

Significance of borderline hemoglobin A2 values in an Italian population with a high prevalence of {beta}-thalassemia

2008-08-29

This study shows that borderline hemoglobin A2 values are not a rare event in a population with a high prevalence of beta-thalassemia carriers. These cases should be investigated at a molecular level, particularly if the partner is a carrier of beta-thalassemia.

Myocardial iron overload assessment by T2* magnetic resonance imaging in adult transfusion dependent patients with acquired anemias

2008-08-29

In this study, gradient echo T2* magnetic resonance imaging provided a rapid and reproducible method for detecting myocardial iron overload which developed after a heavy transfusion burden equal to or greater than 290 mL/kg of packed red blood cell units.

ABL single nucleotide polymorphisms may masquerade as BCR-ABL mutations associated with resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia

2008-08-29

The findings of this study indicate that analysis of normal ABL alleles enables an easy and fast differentiation between single nucleotide polymorphism and acquired mutations of BCR-ABL.

Impaired differentiation and apoptosis of hematopoietic precursors in a mouse model of myelodysplastic syndrome

Choi, C. W., Chung, Y. J., Slape, C., Aplan, P. D. — 2008-08-29

Expression of a NUP98-HOXD13 (NHD13) fusion gene, initially identified in a patient with myelodysplastic syndrome, leads to a highly penetrant myelodysplastic syndrome in mice that recapitulates all of the key features of the human disease. See related perspective article on page 1288.

t(3;11)(q12;p15)/NUP98-LOC348801 fusion transcript in acute myeloid leukemia

2008-08-29

This paper describes molecular cytogenetic findings of a t(3;11)(q12;p15), characterized as a new NUP98 translocation rearranging with LOC348801 at chromosome 3, in a patient with acute myeloid leukemia.

Long-term risk of myelodysplasia in melphalan-treated patients with immunoglobulin light-chain amyloidosis

2008-08-29

In this study, the actuarial risk of myelodysplasia at 10 years was 18% in patients with immunoglobulin light-chain amyloidosis treated with melphalan. As the survival of patients with plasma cell disorders improves, myelodysplasia may be a more common cause of morbidity and mortality for these patients.

Characterization of the -148C>T promoter polymorphism in PKLR

de Vooght, K. M.K., van Wijk, R., van Wesel, A. C., van Solinge, W. W. — 2008-08-29

Molecular studies reveal a concordant KEL genotyping between patients with hemoglobinopathies and blood donors in Sao Paulo City, Brazil

Boturao-Neto, E., Chiba, A. K., Vicari, P., Figueiredo, M. S., Bordin, J. O. — 2008-08-29

Association of asymmetric dimethylarginine with sickle cell disease-related pulmonary hypertension

2008-08-29

Effect of JAK2 V617F on thrombotic risk in patients with essential thrombocythemia: measuring the uncertain

Ziakas, P. D. — 2008-08-29

The seventh pathogenic fusion gene FIP1L1-RARA was isolated from a t(4;17)-positive acute promyelocytic leukemia

Kondo, T., Mori, A., Darmanin, S., Hashino, S., Tanaka, J., Asaka, M. — 2008-08-29

Early discharge from hospital after consolidation chemotherapy in acute myeloid leukemia in remission: febrile neutropenic episodes and their outcome in a resource poor setting

Naithani, R., Kumar, R., Mahapatra, M., Agrawal, N., Mishra, P. — 2008-08-29

Outcome for children with relapsed acute myeloid leukemia in the Netherlands following initial treatment between 1980 and 1998: survival after chemotherapy only?

Goemans, B. F., Tamminga, R. Y.J., Corbijn, C. M., Hahlen, K., Kaspers, G. J.L. — 2008-08-29

The International Prognostic Scoring System for Waldenstrom's macroglobulinemia is applicable in patients treated with rituximab-based regimens

2008-08-29

ZAP-70 mRNA expression provides clinically valuable information in early-stage chronic lymphocytic leukemia

2008-08-29

Epstein-Barr virus reactivation is a potentially severe complication in chronic lymphocytic leukemia patients with poor prognostic biological markers and fludarabine refractory disease

2008-08-29

Rituximab in patients with hairy cell leukemia relapsing after treatment with 2-chlorodeoxyadenosine (SAKK 31/98)

2008-08-29

Increased cytotoxic T-lymphocyte-mediated cytotoxicity predominant in patients with idiopathic thrombocytopenic purpura without platelet autoantibodies

Zhao, C., Li, X., Zhang, F., Wang, L., Peng, J., Hou, M. — 2008-08-29

Elevated factor XIII level and the risk of peripheral artery disease

Shemirani, A. H., Szomjak, E., Csiki, Z., Katona, E., Bereczky, Z., Muszbek, L. — 2008-08-29

Recurrent thromboembolism and major bleeding during oral anticoagulant therapy in patients with solid cancer: findings from the RIETE registry

2008-08-29

Enumeration of cytomegalovirus-specific interferon{gamma} CD8+ and CD4+ T cells early after allogeneic stem cell transplantation may identify patients at risk of active cytomegalovirus infection

2008-08-29

Successful mobilization of hematopoietic peripheral blood progenitor cells with paclitaxel-based chemotherapy as initial or salvage regimen in patients with hematologic malignancies

Fernandez, A., De Arriba, F., Rivera, J., Heras, I., Vicente, V., Lozano, M. L. — 2008-08-29

Sex-specific patterns and trends in the incidence of hematologic malignancies in 0-24 year olds from Northern England, 1968-2005

2008-08-29

Treatment of hepatitis C in patients with thalassemia

Angelucci, E., Pilo, F. — 2008-07-31

Liver disease has long been recognized as an important cause of morbidity and mortality in thalassemia. In this perspective article, Drs. Angelucci and Pilo examine the epidemiology of hepatitis C virus infection in subjects with thalassemia and discuss the current treatment of this condition. See related articles on pages 1243 and 1247.

Treatment of pediatric acute lymphoblastic leukemia

Tucci, F., Arico, M. — 2008-07-31

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. In this perspective article, Drs. Tucci and Aricò discuss advances in the treatment of childhood ALL, which may be regarded as a paradigm of the effectiveness of medical science in treatment of formerly incurable diseases. See related articles on pages 1155 and 1161.

Human immunodeficiency virus-related non-Hodgkin's lymphoma

Ribera, J.-M., Navarro, J.-T. — 2008-07-31

Highly active antiretroviral therapy (HAART) has improved the survival of human immunodeficiency virus (HIV)-infected patients dramatically. Nonetheless, HIV-related lymphomas still constitute a major cause of death in HIV-infected patients. In this perspective article, Drs. Ribera and Navarro, examine this serious complication of AIDS. See related article on page 1178.

Cardiovascular disease after hematopoietic cell transplantation - lessons learned

Armenian, S. H., Bhatia, S. — 2008-07-31

Due to improvements in survival rate, major issues in patients undergoing hematopoietic stem cell transplantation have expanded to include the care and management of survivors, prevention of adverse outcomes, and maintenance of a good quality of life. In this perspective article, Drs. Armenian and Bathia discuss cardiovascular dysfunction, which is now emerging as a late complication of hematopoietic stem cell transplantation. See related article on page 1203.

CD97 is differentially expressed on murine hematopoietic stem-and progenitor-cells

van Pel, M., Hagoort, H., Hamann, J., Fibbe, W. E. — 2008-07-31

CD97 is a member of the epidermal growth factor-seven transmembrane (EGF-TM7) receptor family. This study shows that murine hematopoietic cells expressing high levels of c-Kit and intermediate levels of CD97 have repopulating and radioprotective capacity. This phenotype allows simple and rapid purification of murine hematopoietic stem cells.

Centrosome aberrations and G1 phase arrest after in vitro and in vivo treatment with the SRC/ABL inhibitor dasatinib

2008-07-31

Dasatinib is an ATP-competitive, dual SRC/ABL kinase inhibitor with antiproliferative activity. It is approved for the treatment of adult patients with chronic myeloid leukemia with resistance or intolerance to prior therapy including imatinib mesylate, and for the treatment of patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy. This study shows that dasatinib blocks G₁/S transition and thereby inhibits cell growth in both normal and neoplastic cells. In addition, it induces centrosomal aberrations and decreases mitotic spindles. These effects may be the result of a combination of SRC and ABL inhibition.

Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Group Study L99-15

2008-07-31

Early treatment response is one of the most useful prognostic indicators in childhood acute lymphoblastic leukemia. This study adds novel information that patients whose peripheral blood blasts disappeared after 7 days of prednisolone monotherapy had an excellent prognosis, that is, a 4-year event-free survival of 90%. See related perspective article on page 1124.

Acute lymphoblastic leukemia in adolescents and young adults in Finland

2008-07-31

Recent reports indicate that adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric rather than adult therapeutic protocols. This Finnish study did not show any major difference between patients treated with pediatric protocols and those treated with adult protocols, but confirmed that adolescents and young adults with acute lymphoblastic leukemia still have a poorer outcome than children below 10 years of age. See related perspective article on page 1124.

The prevention of spontaneous apoptosis of follicular lymphoma B cells by a follicular dendritic cell line: involvement of caspase-3, caspase-8 and c-FLIP

2008-07-31

Several observations point to a crucial role of microenvironment in the natural history of low-grade B-cell neoplasms. This study shows that the spontaneous apoptosis of follicular lymphoma cells is partially prevented by a follicular dendritic cell line, thus confirming that cellular microenvironment may contribute to the development and/or progression of follicular lymphoma cells.

Molecular analysis of immunoglobulin variable genes in human immunodeficiency virus-related non-Hodgkin's lymphoma reveals implications for disease pathogenesis and histogenesis

2008-07-31

Non-Hodgkin’s lymphomas are a major complication of human immunodeficiency virus (HIV) infection and include heterogeneous conditions. This study shows evidence of a skewed IGHV repertoire in specific categories and suggests B-cell receptor restriction in some HIV-primary central nervous system lymphomas. See related perspective article on page 1129.

Somatic hypermutation signature in B-cell low-grade lymphomas

2008-07-31

Immunoglobulin gene somatic hypermutation (SHM) is a biologically relevant and clinically useful prognostic factor in different types of low-grade B-cell lymphomas. This study of gene expression profiling identified a large number of genes that may be surrogate markers of the SHM process.

De novo CD5+ diffuse large B-cell lymphoma: results of a detailed clinicopathological review in 120 patients

2008-07-31

Diffuse large B-cell lymphoma (DLBCL) constitutes the largest category of aggressive lymphomas, and is considered to have heterogeneous biological properties. De novo CD5-positive diffuse large B-cell lymphoma (CD5⁺ DLBCL) is a distinct entity. This study reveals the morphological spectrum of CD5⁺ DLBCL, shows that the incidence of central nervous system recurrence in this form of lymphoma in high, and confirms that CD5⁺ DLBCL frequently expresses BCL2 protein.

Late cardiovascular events after allogeneic hematopoietic stem cell transplantation: a retrospective multicenter study of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation

2008-07-31

Long-term outcome after hematopoietic stem cell transplantation including late transplant-related events is of increasing interest. This study shows that long-term survivors after allogeneic hematopoietic stem cell transplantation are likely to have an increased risk of premature cardiovascular accidents. See related perspective article on page 1132.

A new severity score index for phenotypic classification and evaluation of responses to treatment in type I Gaucher disease

2008-07-31

Gaucher disease is the first lysosomal storage disease for which specific therapy became available. This study reports a reliable method for staging the severity of adult type I Gaucher disease, and for monitoring the response to treatment.

A one-mutation mathematical model can explain the age incidence of acute myeloid leukemia with mutated nucleophosmin (NPM1)

2008-07-31

Acute myeloid leukemia with mutated NPM1 gene and aberrant cytoplasmic expression of nucleophosmin shows distinctive biological and clinical features. Based on the use of a one-mutation mathematical model, this study supports the hypothesis that a single genetic event, the NPM1 mutation, is sufficient to cause this type of leukemia.

The postoperative splenic/portal vein thrombosis after splenectomy and its prevention - an unresolved issue

Krauth, M.-T., Lechner, K., Neugebauer, E. A.M., Pabinger, I. — 2008-07-31

Patients undergoing splenectomy have an increased risk of splenic/portal vein thrombosis. This study shows that the overall risk is 3.3%. Risk factors are big spleens and hereditary hemolytic anemias.

CXCR4pos circulating progenitor cells coexpressing monocytic and endothelial markers correlating with fibrotic clinical features are present in the peripheral blood of patients affected by systemic sclerosis

2008-07-31

This study shows that patients with systemic sclerosis have an increased number of CXCR4^pos circulating progenitor cells coexpressing monocytic and endothelial markers.