Editorials and Perspectives:

Kushang V. Patel

Variability and heritability of hemoglobin concentration: an opportunity to improve understanding of anemia in older adults
Haematologica 2008 93: 1281-1283. [Full Text] [PDF]  

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.

Achille Iolascon, Rosa Anna Avvisati

Genotype/phenotype correlation in hereditary spherocytosis
Haematologica 2008 93: 1283-1288. [Full Text] [PDF]  

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.

Michaela Fontenay, Emmanuel Gyan

Apoptotic pathways to death in myelodysplastic syndromes
Haematologica 2008 93: 1288-1292. [Full Text] [PDF]  

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.

Martin Janz, Stephan Mathas

The pathogenesis of classical Hodgkin’s lymphoma: what can we learn from analyses of genomic alterations in Hodgkin and Reed-Sternberg cells?
Haematologica 2008 93: 1292-1295. [Full Text] [PDF]  

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.

Gösta Gahrton, Bo Björkstrand

Allogeneic transplantation in multiple myeloma
Haematologica 2008 93: 1295-1300. [Full Text] [PDF]  

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.

Original Articles:

Hematopoiesis:

Soraya Tabera, José A. Pérez-Simón, María Díez-Campelo, Luis I. Sánchez-Abarca, Belén Blanco, Antonio López, Ana Benito, Enrique Ocio, Fermín M. Sánchez-Guijo, Consuelo Cañizo, Jesús F. San Miguel

The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes
Haematologica 2008 93: 1301-1309. Published online July 18, 2008; doi:10.3324/haematol.12857 [Abstract] [Full Text] [PDF]  

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.

Red Cell Disorders:

Mariagabriella Mariani, Wilma Barcellini, Cristina Vercellati, Anna Paola Marcello, Elisa Fermo, Paola Pedotti, Carla Boschetti, Alberto Zanella

Clinical and hematologic features of 300 patients affected by hereditary spherocytosis grouped according to the type of the membrane protein defect
Haematologica 2008 93: 1310-1317. Published online July 18, 2008; doi:10.3324/haematol.12546 [Abstract] [Full Text] [PDF]  

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.

Malignant Lymphomas:

Sylvia Hartmann, José I. Martin-Subero, Stefan Gesk, Julia Hüsken, Maciej Giefing, Inga Nagel, Jennifer Riemke, Andreas Chott, Wolfram Klapper, Marie Parrens, Jean-Philippe Merlio, Ralf Küppers, Andreas Bräuninger, Reiner Siebert, Martin-Leo Hansmann

Detection of genomic imbalances in microdissected Hodgkin and Reed-Sternberg cells of classical Hodgkin’s lymphoma by array-based comparative genomic hybridization
Haematologica 2008 93: 1318-1326. Published online July 18, 2008; doi:10.3324/haematol.12875 [Abstract] [Full Text] [PDF] [Hartmann et al. - Supplementary Appendix]  

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.

Itziar Salaverria, Andreas Zettl, Silvia Beà, Elena M. Hartmann, Sandeep S. Dave, George W. Wright, Evert-Jan Boerma, Philip M. Kluin, German Ott, Wing C. Chan, Dennis D. Weisenburger, Armando Lopez-Guillermo, Randy D. Gascoyne, Jan Delabie, Lisa M. Rimsza, Rita M. Braziel, Elaine S. Jaffe, Louis M. Staudt, Hans Konrad Müller-Hermelink, Elias Campo, Andreas Rosenwald, for the Leukemia and Lymphoma Molecular Profiling Project (LLMPP)

Chromosomal alterations detected by comparative genomic hybridization in subgroups of gene expression-defined Burkitt’s lymphoma
Haematologica 2008 93: 1327-1334. Published online August 12, 2008; doi:10.3324/haematol.13071 [Abstract] [Full Text] [PDF]  

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.

Stefano Sacchi, Luigi Marcheselli, Alessia Bari, Raffaella Marcheselli, Samantha Pozzi, Paolo G. Gobbi, Francesco Angrilli, Maura Brugiatelli, Pellegrino Musto, Massimo Federico

Second malignancies after treatment of diffuse large B-cell non-Hodgkin’s lymphoma: a GISL cohort study
Haematologica 2008 93: 1335-1342. Published online August 12, 2008; doi:10.3324/haematol.12918 [Abstract] [Full Text] [PDF]  

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.

Multiple Myeloma:

Francis Ayuk, José A. Perez-Simon, Avichai Shimoni, Anna Sureda, Tatjana Zabelina, Rainer Schwerdtfeger, Rodrigo Martino, Herbert Gottfried Sayer, Adrián Alegre, Juan-José Lahuerta, Djordje Atanackovic, Christine Wolschke, Arnon Nagler, Axel R. Zander, Jesús F. San Miguel, Nicolaus Kröger

Clinical impact of human Jurkat T-cell-line-derived antithymocyte globulin in multiple myeloma patients undergoing allogeneic stem cell transplantation
Haematologica 2008 93: 1343-1350. Published online July 18, 2008; doi:10.3324/haematol.12665 [Abstract] [Full Text] [PDF]  

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.

Disorders of Hemostasis:

Arne W.J.H. Dielis, Wolfgang M.R. Balliël, René van Oerle, Wim T. Hermens, Henri M.H. Spronk, Hugo ten Cate, Karly Hamulyák

Thrombomodulin-modified thrombin generation after in vivo recombinant factor VIII treatment in severe hemophilia A
Haematologica 2008 93: 1351-1357. Published online July 18, 2008; doi:10.3324/haematol.13039 [Abstract] [Full Text] [PDF]  

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.

Thrombosis:

Pilar Medina, Silvia Navarro, Javier Corral, Esther Zorio, Vanessa Roldán, Amparo Estellés, Amparo Santamaría, Francisco Marín, Joaquín Rueda, Rogier M. Bertina, Francisco España, for the RECAVA Thrombosis Groups

Endothelial protein C receptor polymorphisms and risk of myocardial infarction
Haematologica 2008 93: 1358-1363. [Abstract] [Full Text] [PDF]  

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.

Decision Making and Problem Solving:

Pier Luigi Zinzani, Maurizio Martelli, Venerino Poletti, Umberto Vitolo, Paolo G. Gobbi, Tommaso Chisesi, Giovanni Barosi, Andrés J.M. Ferreri, Monia Marchetti, Nicola Pimpinelli, Sante Tura

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
Haematologica 2008 93: 1364-1371. Published online July 4, 2008; doi:10.3324/haematol.12742 [Abstract] [Full Text] [PDF]  

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.

Brief Report:

Erythropoiesis:

Cinzia Sala, Marina Ciullo, Carmela Lanzara, Teresa Nutile, Silvia Bione, Roberto Massacane, Pio d’Adamo, Paolo Gasparini, Daniela Toniolo, Clara Camaschella

Variation of hemoglobin levels in normal Italian populations from genetic isolates
Haematologica 2008 93: 1372-1375. Published online July 4, 2008; doi:10.3324/haematol.12915 [Abstract] [Full Text] [PDF] [Sala et al. Supplementary appendix]  

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.

Kathryn W. Woodburn, Susan D. Wilson, Kei-lai Fong, Peter J. Schatz, Thomas Ferrell, Charles B. Spainhour, Daniel Norton

Chronic preclinical safety evaluation of Hematide^TM, a pegylated peptidic erythropoiesis stimulating agent in monkeys
Haematologica 2008 93: 1376-1379. Published online June 2, 2008; doi:10.3324/haematol.12896 [Abstract] [Full Text] [PDF]  

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.

Thalassemia Syndromes:

Antonino Giambona, Cristina Passarello, Margherita Vinciguerra, Rita Li Muli, Pietro Teresi, Maurizio Anzà, Gaetano Ruggeri, Disma Renda, Aurelio Maggio

Significance of borderline hemoglobin A2 values in an Italian population with a high prevalence of β-thalassemia
Haematologica 2008 93: 1380-1384. Published online July 4, 2008; doi:10.3324/haematol.12840 [Abstract] [Full Text] [PDF]  

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.

Anna Angela Di Tucci, Gildo Matta, Simona Deplano, Attilio Gabbas, Cristina Depau, Daniele Derudas, Giovanni Caocci, Annalisa Agus, Emanuele Angelucci

Myocardial iron overload assessment by T2* magnetic resonance imaging in adult transfusion dependent patients with acquired anemias
Haematologica 2008 93: 1385-1388. Published online July 4, 2008; doi:10.3324/haematol.12759 [Abstract] [Full Text] [PDF]  

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.

Chronic Myeloid Leukemia:

Thomas Ernst, Jana Hoffmann, Philipp Erben, Benjamin Hanfstein, Armin Leitner, Rüdiger Hehlmann, Andreas Hochhaus, Martin C. Müller

ABL single nucleotide polymorphisms may masquerade as BCR-ABL mutations associated with resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia
Haematologica 2008 93: 1389-1393. Published online July 4, 2008; doi:10.3324/haematol.12964 [Abstract] [Full Text] [PDF] [Ernst et al. . Supplementary appendix]  

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.

Myelodysplastic Syndromes:

Chul Won Choi, Yang Jo Chung, Christopher Slape, Peter D. Aplan

Impaired differentiation and apoptosis of hematopoietic precursors in a mouse model of myelodysplastic syndrome
Haematologica 2008 93: 1394-1397. Published online July 4, 2008; doi:10.3324/haematol.13042 [Abstract] [Full Text] [PDF]  

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.

Acute Myeloid Leukemia:

Paolo Gorello, Lucia Brandimarte, Roberta La Starza, Valentina Pierini, Loredana Bury, Roberto Rosati, Massimo F. Martelli, Peter Vandenberghe, Iwona Wlodarska, Cristina Mecucci

t(3;11)(q12;p15)/NUP98-LOC348801 fusion transcript in acute myeloid leukemia
Haematologica 2008 93: 1398-1401. Published online July 4, 2008; doi:10.3324/haematol.12945 [Abstract] [Full Text] [PDF]  

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.

Multiple Myeloma:

Morie A. Gertz, Martha Q. Lacy, John A. Lust, Philip R. Greipp, Thomas E. Witzig, Robert A. Kyle

Long-term risk of myelodysplasia in melphalan-treated patients with immunoglobulin light-chain amyloidosis
Haematologica 2008 93: 1402-1406. Published online July 18, 2008; doi:10.3324/haematol.12982 [Abstract] [Full Text] [PDF]  

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.

Letters to the Editor:

Red Cell Disorders:

Karen M.K. de Vooght, Richard van Wijk, Annet C. van Wesel, Wouter W. van Solinge

Characterization of the –148C>T promoter polymorphism in PKLR
Haematologica 2008 93: 1407-1408. Published online August 12, 2008; doi:10.3324/haematol.12328 [Full Text] [PDF]  

Edmir Boturão-Neto, Akemi K. Chiba, Perla Vicari, Maria S. Figueiredo, José O. Bordin

Molecular studies reveal a concordant KEL genotyping between patients with hemoglobinopathies and blood donors in São Paulo City, Brazil
Haematologica 2008 93: 1408-1410. Published online July 4, 2008; doi:10.3324/haematol.12766 [Full Text] [PDF]  

Precious P. Landburg, Tom Teerlink, Eduard J. van Beers, Frits A.J. Muskiet, Mies C. Kappers-Klunne, Joost W.J. van Esser, Melvin R. Mac Gillavry, Bart J. Biemond, Dees P.M. Brandjes, Ashley J. Duits, John-John Schnog on behalf of the CURAMA study group

Association of asymmetric dimethylarginine with sickle cell disease-related pulmonary hypertension
Haematologica 2008 93: 1410-1412. Published online July 18, 2008; doi:10.3324/haematol.12928 [Full Text] [PDF] [Landburg et al. - Supplementary appendix]  

Myeloproliferative Disorders:

Panayiotis D. Ziakas

Effect of JAK2 V617F on thrombotic risk in patients with essential thrombocythemia: measuring the uncertain
Haematologica 2008 93: 1412-1414. Published online July 18, 2008; doi:10.3324/haematol.12970 [Full Text] [PDF] [Ziakas et al. - Supplementary appendix]  

Acute Promyelocytic Leukemia:

Takeshi Kondo, Akio Mori, Stephanie Darmanin, Satoshi Hashino, Junji Tanaka, Masahiro Asaka

The seventh pathogenic fusion gene FIP1L1-RARA was isolated from a t(4;17)-positive acute promyelocytic leukemia
Haematologica 2008 93: 1414-1416. Published online July 4, 2008; doi:10.3324/haematol.12854 [Full Text] [PDF]  

Acute Myeloid Leukemia:

Rahul Naithani, Rajat Kumar, Manoranjan Mahapatra, Neerja Agrawal, Pravas Mishra

Early discharge from hospital after consolidation chemotherapy in acute myeloid leukemia in remission: febrile neutropenic episodes and their outcome in a resource poor setting
Haematologica 2008 93: 1416-1418. Published online July 4, 2008; doi:10.3324/haematol.11696 [Full Text] [PDF]  

Bianca F. Goemans, Rienk Y.J. Tamminga, Carin M. Corbijn, Karel Hählen, GertJan J.L. Kaspers

Outcome for children with relapsed acute myeloid leukemia in the Netherlands following initial treatment between 1980 and 1998: survival after chemotherapy only?
Haematologica 2008 93: 1418-1420. Published online August 12, 2008; doi:10.3324/haematol.12807. [Full Text] [PDF]  

Malignant Lymphomas:

Meletios Athanasios Dimopoulos, Efstathios Kastritis, Sossana Delimpassi, Athanasios Zomas, Marie Christine Kyrtsonis, Konstantinos Zervas

The International Prognostic Scoring System for Waldenström’s macroglobulinemia is applicable in patients treated with rituximab-based regimens
Haematologica 2008 93: 1420-1422. Published online July 18, 2008; doi:10.3324/haematol.12846 [Full Text] [PDF]  

Lymphoproliferative Disorders:

Cristina Reinoso-Martín, Eloisa Jantus-Lewintre, Carlos García Ballesteros, Carmen Benet Campos, José Ramón Mayans Ferrer, Javier García-Conde

ZAP-70 mRNA expression provides clinically valuable information in early-stage chronic lymphocytic leukemia
Haematologica 2008 93: 1422-1424. [Full Text] [PDF]  

Julie Rath, Christian Geisler, Claus B. Christiansen, Nina Hastrup, Hans O. Madsen, Mette K. Andersen, Lone B. Pedersen, Jesper Jurlander

Epstein-Barr virus reactivation is a potentially severe complication in chronic lymphocytic leukemia patients with poor prognostic biological markers and fludarabine refractory disease
Haematologica 2008 93: 1424-1426. Published online July 18, 2008; doi:10.3324/haematol.13059 [Full Text] [PDF]  

Reinhard Zenhäusern, Mathew Simcock, Alois Gratwohl, Urs Hess, Mario Bargetzi, Andreas Tobler on behalf of the Swiss Group for Clinical Cancer Research (SAKK)

Rituximab in patients with hairy cell leukemia relapsing after treatment with 2-chlorodeoxyadenosine (SAKK 31/98)
Haematologica 2008 93: 1426-1428. Published online July 4, 2008; doi:10.3324/haematol.11564 [Full Text] [PDF]  

Platelet Disorders:

Chunhong Zhao, Xiaofang Li, Feng Zhang, Lin Wang, Jun Peng, Ming Hou

Increased cytotoxic T-lymphocyte-mediated cytotoxicity predominant in patients with idiopathic thrombocytopenic purpura without platelet autoantibodies
Haematologica 2008 93: 1428-1430. Published online August 12, 2008; doi:10.3324/haematol.12889. [Full Text] [PDF]  

Thrombosis:

Amir H. Shemirani, Edit Szomják, Zoltán Csiki, Éva Katona, Zsuzsanna Bereczky, László Muszbek

Elevated factor XIII level and the risk of peripheral artery disease
Haematologica 2008 93: 1430-1432. Published online July 4, 2008; doi:10.3324/haematol.12708 [Full Text] [PDF]  

Paolo Prandoni, Javier Trujillo-Santos, Teresa Surico, Fabio Dalla Valle, Andrea Piccioli, Manuel Monreal, for the RIETE Investigators

Recurrent thromboembolism and major bleeding during oral anticoagulant therapy in patients with solid cancer: findings from the RIETE registry
Haematologica 2008 93: 1432-1434. [Full Text] [PDF]  

Stem Cell Transplantation:

Carlos Solano, Isana Benet, María A. Clari, José Nieto, Rafael de la Cámara, Javier López, Juan C. Hernández-Boluda, María J. Remigia, Isidro Jarque, María L. Calabuig, Ana Garcia-Noblejas, Juan Alberola, Amparo Tamarit, Concepción Gimeno, David Navarro

Enumeration of cytomegalovirus-specific interferon CD8⁺ and CD4⁺ T cells early after allogeneic stem cell transplantation may identify patients at risk of active cytomegalovirus infection
Haematologica 2008 93: 1434-1436. Published online July 4, 2008; doi:10.3324/haematol.12880 [Full Text] [PDF]  

Angel Fernández, Felipe De Arriba, José Rivera, Inmaculada Heras, Vicente Vicente, María Luisa Lozano

Successful mobilization of hematopoietic peripheral blood progenitor cells with paclitaxel-based chemotherapy as initial or salvage regimen in patients with hematologic malignancies
Haematologica 2008 93: 1436-1438. Published online July 18, 2008; doi:10.3324/haematol.13056 [Full Text] [PDF]  

Epidemiology:

Brooke L. Magnanti, M. Tevfik Dorak, Louise Parker, Alan W. Craft, Peter W. James, Richard J.Q. McNally

Sex-specific patterns and trends in the incidence of hematologic malignancies in 0–24 year olds from Northern England, 1968–2005
Haematologica 2008 93: 1438-1440. Published online July 4, 2008; doi:10.3324/haematol.12919 [Full Text] [PDF]  

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