Editorials and Perspectives:

Pierre M. Durand, Theresa L. Coetzer

Hereditary red cell disorders and malaria resistance
Haematologica 2008 93: 961-963. [Full Text] [PDF]  

In this perspective article, Drs. Durand and Coetzer review evidence strongly indicating that pyruvate kinase deficiency evolved as a protective response to malaria. See also their recent contribution in this journal [Durand PM, Coetzer TL. Pyruvate kinase deficiency protects against malaria in humans. Haematologica 2008; 93:939–40. Epub 2008 May 6].

Melanie J. Percy, Frank S. Lee

Familial erythrocytosis: molecular links to red blood cell control
Haematologica 2008 93: 963-967. [Full Text] [PDF]  

Familial or hereditary erythrocytosis is a rare disorder of red cell production that can be inherited in either an autosomal dominant or recessive fashion. In this perspective article, Drs. Percy and Lee illustrate how identification of molecular lesions as the basis of erythrocytosis has provided a compelling correlation with, and indeed, physiological validation of proteins implicated in the pathway that senses oxygen and signals to erythropoiesis. Very interestingly, they show that all of the major elements in the oxygen sensing pathway have now been accounted for in the current OMIM classification of familial erythrocytoses. See related articles on pages 1068 and 1072.

Mario Cazzola

Myelodysplastic syndrome with isolated 5q deletion (5q- syndrome). A clonal stem cell disorder characterized by defective ribosome biogenesis
Haematologica 2008 93: 967-972. [Full Text] [PDF]  

The 5q- syndrome was first described by van den Berghe and co-workers in 1974. In this perspective article, Dr. Cazzola discusses its clonal nature and examines recent findings indicating that haploinsufficiency of genes mapping to chromosome 5q31–q32 leads to aberrant ribosome biogenesis. Dr. Cazzola also discusses the current uncertainties on the use of lenalidomide for treatment of myelodysplastic syndrome with deletion 5q. See related articles on pages 994 and 1001.

Alessandro M. Vannucchi, Paola Guglielmelli

Molecular pathophysiology of Philadelphia-negative myeloproliferative disorders: beyond JAK2 and MPL mutations
Haematologica 2008 93: 972-976. [Full Text] [PDF]  

The discovery of the JAK2 and MPL mutations has been of enormous help in the diagnosis and characterization of chronic myeloproliferative disorders, and has opened new perspectives for targeted therapy. In this perspective article, Drs. Vannucchi and Guglielmelli review additional molecular mechanisms that may contribute to the pathogenesis of these disorders, such as aberrant expression of microRNA. See related papers on pages 1009 and 1098.

Konstanze Döhner, Hartmut Döhner

Molecular characterization of acute myeloid leukemia
Haematologica 2008 93: 976-982. [Full Text] [PDF]  

Acute myeloid leukemia is a genetically heterogeneous c lonal disorder characterized by the accumulation of acquired somatic genetic alterations in hematopoietic progenitor cells that alter normal mechanisms of self-renewal, proliferation and differentiation. In this perspective article, Drs. K. Döhner and H. Döhner examine the molecular basis of acute myeloid leukemia and the prognostic relevance of mutations of genes such a NPM1, FLT3 and CEBPA. See related papers on pages 1017 and 1025.

Nathalie A. Johnson, Randy D. Gascoyne

Gene expression signatures in follicular lymphoma: are they ready for the clinic?
Haematologica 2008 93: 982-987. [Full Text] [PDF]  

In this perspective article, Drs. Johnson and Gascoyne discuss clinical translation of gene expression signatures in follicular lymphoma. Genome-wide microarray studies offer a powerful discovery tool and should be built into the design of phase III clinical trials in follicular lymphoma. See related article on page 1033.

Original Articles:

Red Cell Disorders:

Isabelle Berthaut, Geoffroy Guignedoux, Frederique Kirsch-Noir, Vanina de Larouziere, Celia Ravel, Dora Bachir, Frédéric Galactéros, Pierre-Yves Ancel, Jean-Marie Kunstmann, Laurence Levy, Pierre Jouannet, Robert Girot, Jacqueline Mandelbaum

Influence of sickle cell disease and treatment with hydroxyurea on sperm parameters and fertility of human males
Haematologica 2008 93: 988-993. Published online May 27, 2008; doi:10.3324/haematol.11515 [Abstract] [Full Text] [PDF]  

The use of hydroxyurea has considerably modified the prognosis of sickle cell disease and many more patients now reach reproductive age. This study shows alterations of semen parameters due to sickle cell disease that seem to be exacerbated by hydroxyurea treatment. The authors suggest that a pre-treatment sperm analysis be performed and sperm cryopreservation be offered to patients before hydroxyurea treatment.

Myelodysplastic Syndromes:

Li Wang, Carrie Fidler, Nandita Nadig, Aristoteles Giagounidis, Matteo G. Della Porta, Luca Malcovati, Sally Killick, Norbert Gattermann, Carlo Aul, Jacqueline Boultwood, James S. Wainscoat

Genome-wide analysis of copy number changes and loss of heterozygosity in myelodysplastic syndrome with del(5q) using high-density single nucleotide polymorphism arrays
Haematologica 2008 93: 994-1000. Published online May 27, 2008; doi:10.3324/haematol.12603 [Abstract] [Full Text] [PDF] [Wang et al. - Supplementary Appendix]  

This study shows a clear distinction between 5q- syndrome and other cases of myelodysplastic syndrome with del(5q) with regards to both copy number changes and the presence of large uniparental disomy, consistent with the different clinical behavior of patients with these two disorders. See related perspective on page 967.

Mar Mallo, Leonor Arenillas, Blanca Espinet, Marta Salido, Jesús Mª Hernández, Eva Lumbreras, Mónica del Rey, Eva Arranz, Soraya Ramiro, Patricia Font, Olga González, Mónica Renedo, José Cervera, Esperanza Such, Guillermo F. Sanz, Elisa Luño, Carmen Sanzo, Miriam González, María José Calasanz, José Mayans, Carlos García-Ballesteros, Victoria Amigo, Rosa Collado, Isabel Oliver, Félix Carbonell, Encarna Bureo, Andrés Insunza, Lucrecia Yañez, María José Muruzabal, Elena Gómez-Beltrán, Rafael Andreu, Pilar León, Valle Gómez, Ángeles Sanz, Natalia Casasola, Esperanza Moreno, Adrián Alegre, María Luisa Martín, Carmen Pedro, Sergi Serrano, Lourdes Florensa, Francesc Solé

Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-
Haematologica 2008 93: 1001-1008. [Abstract] [Full Text] [PDF]  

The findings of this study indicate that fluorescence in situ hybridization improves the detection of deletion 5q31–32 in patients with myelodysplastic syndrome without cytogenetic evidence of del(5q). See related perspective on page 967.

Myeloproliferative Disorders:

Hana Bruchova, Michaela Merkerova, Josef T. Prchal

Aberrant expression of microRNA in polycythemia vera
Haematologica 2008 93: 1009-1016. Published online May 27, 2008; doi:10.3324/haematol.12706 [Abstract] [Full Text] [PDF] [Bruchova et al. - Supplementary Appendix]  

The findings of this study indicate that peripheral blood cells from patients with polycythemia vera have microRNA signatures distinct from those of controls, underlining the complexity of the molecular basis of myeloproliferative disorders. See related perspective on page 972.

Acute Myeloid Leukemia:

Francesco Lo-Coco, Antonio Cuneo, Fabrizio Pane, Daniela Cilloni, Daniela Diverio, Marco Mancini, Nicoletta Testoni, Antonella Bardi, Barbara Izzo, Niccolò Bolli, Roberta La Starza, Paola Fazi, Simona Iacobelli, Alfonso Piciocchi, Marco Vignetti, Sergio Amadori, Franco Mandelli, Pier Giuseppe Pelicci, Cristina Mecucci, Brunangelo Falini, Giuseppe Saglio, for the Acute Leukemia Working Party of the GIMEMA group

Prognostic impact of genetic characterization in the GIMEMA LAM99P multicenter study for newly diagnosed acute myeloid leukemia
Haematologica 2008 93: 1017-1024. Published online May 27, 2008; doi:10.3324/haematol.12004 [Abstract] [Full Text] [PDF]  

The findings of this study reiterate the prognostic relevance of combining cytogenetic and mutational analysis (NPM1, FTT3) in the diagnostic work up of acute myeloid leukemia. See related perspective on page 976.

Alessandro Pulsoni, Simona Iacobelli, Massimo Bernardi, Marco Borgia, Andrea Camera, Nicola Cantore, Francesco Di Raimondo, Paola Fazi, Felicetto Ferrara, Franco Leoni, Vincenzo Liso, Marco Mancini, Filippo Marmont, Angela Matturro, Luca Maurillo, Lorella Melillo, Giovanna Meloni, Salvo Mirto, Giorgina Specchia, Caterina Giovanna Valentini, Adriano Venditti, Giuseppe Leone, Robin Foà, Franco Mandelli, Livio Pagano

M4 acute myeloid leukemia: the role of eosinophilia and cytogenetics in treatment response and survival. The GIMEMA experience
Haematologica 2008 93: 1025-1032. Published online May 27, 2008; doi:10.3324/haematol.11889 [Abstract] [Full Text] [PDF]  

This analysis on a large GIMEMA population of patients with M4-acute myeloid leukemia confirmed the favorable prognostic role of inv(16), demonstrated the good prognostic role of eosinophilia and revealed an enhancement of the effect when the two factors were both present. See related perspective on page 976.

Malignant Lymphomas:

Pier Paolo Piccaluga, Andrea Califano, Ulf Klein, Claudio Agostinelli, Beatriz Bellosillo, Eva Gimeno, Sergi Serrano, Francisco Solè, Yonghui Zang, Brunangelo Falini, Pier Luigi Zinzani, Stefano A. Pileri

Gene expression analysis provides a potential rationale for revising the histological grading of follicular lymphomas
Haematologica 2008 93: 1033-1038. Published online May 19, 2008; doi:10.3324/haematol.12754 [Abstract] [Full Text] [PDF] [Piccaluga et al. - Supplementary Appendix]  

The findings of this study support the hypothesis that grade IIIb follicular lymphoma belongs to the group of follicular lymphomas rather than to diffuse large B-cell lymphomas. See related perspective on page 982.

Lymphoproliferative Disorders:

Simona Romano, Maria Mallardo, Federico Chiurazzi, Rita Bisogni, Anna D’Angelillo, Raffaele Liuzzi, Giovanna Compare, Maria Fiammetta Romano

The effect of FK506 on transforming growth factor β signaling and apoptosis in chronic lymphocytic leukemia B cells
Haematologica 2008 93: 1039-1048. Published online May 19, 2008; doi:10.3324/haematol.12402 [Abstract] [Full Text] [PDF]  

Loss of response to transforming growth factor-β (TGF-β) is thought to contribute to the progression of chronic lymphocytic leukemia. This study shows that chronic lymphocytic leukemia cells do indeed escape the homeostatic control of TGF-β.

Multiple Myeloma:

Henk Rozemuller, Ellen van der Spek, Lijnie H. Bogers-Boer, Mieke C. Zwart, Vivienne Verweij, Maarten Emmelot, Richard W. Groen, Robbert Spaapen, Andries C. Bloem, Henk M. Lokhorst, Tuna Mutis, Anton C. Martens

A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect
Haematologica 2008 93: 1049-1057. Published online May 19, 2008; doi:10.3324/haematol.12349 [Abstract] [Full Text] [PDF]  

The development and preclinical testing of novel immunotherapy strategies for multiple myeloma can benefit substantially from a humanized animal model that enables quantitative real-time monitoring of tumor progression. This study describes a non-invasive bioluminescent imaging system for real-time monitoring of multiple myeloma cell growth in mice.

Transfusion Medicine:

Agata Drewniak, Jaap-Jan Boelens, Hans Vrielink, Anton T.J. Tool, Marrie C.A. Bruin, Marry van den Heuvel-Eibrink, Lynne Ball, Marianne D. van de Wetering, Dirk Roos, Taco W. Kuijpers

Granulocyte concentrates: prolonged functional capacity during storage in the presence of phenotypic changes
Haematologica 2008 93: 1058-1067. Published online May 27, 2008; doi:10.3324/haematol.12489 [Abstract] [Full Text] [PDF] [Drewniak et al. - Supplementary Appendix]  

Granulocyte transfusions may be an effective therapy for neutropenic pediatric patients suffering from life-threatening infections. This study shows that granulocyte concentrates can be stored without loss of in vitro viability and functionality for at least 24 hours.

Brief Report:

Erythrocytosis:

Maurizio Martini, Luciana Teofili, Tonia Cenci, Fiorina Giona, Lorenza Torti, Massimiliano Rea, Robin Foà, Giuseppe Leone, Luigi Maria Larocca

A novel heterozygous HIF2A^M535I mutation reinforces the role of oxygen sensing pathway disturbances in the pathogenesis of familial erythrocytosis
Haematologica 2008 93: 1068-1071. Published online May 27, 2008; doi:10.3324/haematol.13210 [Abstract] [Full Text] [PDF] [Martini et al. - Supplementary Appendix]  

This report shows that two members of a family with idiopathic erythrocytosis carried a mutation in the hypoxia-inducible factor-2A (HIF2A) gene. See related perspective article on page 963.

Maha Al-Sheikh, Elodie Mazurier, Betty Gardie, Nicole Casadevall, Frédéric Galactéros, Michel Goossens, Henri Wajcman, Claude Préhu, Valérie Ugo

A study of 36 unrelated cases with pure erythrocytosis revealed three new mutations in the erythropoietin receptor gene
Haematologica 2008 93: 1072-1075. Published online May 19, 2008; doi:10.3324/haematol.12260 [Abstract] [Full Text] [PDF]  

This report describes new mutations in the erythropoietin receptor (EPOR) gene in patients with erythrocytosis of unknown origin. See related perspective article on page 963.

Acute Myeloid Leukemia:

Nuno Cerveira, Francesca Micci, Joana Santos, Manuela Pinheiro, Cecília Correia, Susana Lisboa, Susana Bizarro, Lucília Norton, Anders Glomstein, Ann E. Åsberg, Sverre Heim, Manuel R. Teixeira

Molecular characterization of the MLL-SEPT6 fusion gene in acute myeloid leukemia: identification of novel fusion transcripts and cloning of genomic breakpoint junctions
Haematologica 2008 93: 1076-1080. Published online May 19, 2008; doi:10.3324/haematol.12594 [Abstract] [Full Text] [PDF] [Cerveira et al. - Supplementary Appendix]  

This report describes a detailed RNA and DNA analysis in three new patients with acute myeloid leukemia carrying the MLL-SEPT6 rearrangement.

Lymphoproliferative Disorders:

Xinying Su, Véronique Della-Valle, Eric Delabesse, Zahia Azgui, Roland Berger, Hélène Merle-Béral, Olivier A Bernard, Florence Nguyen-Khac

Transcriptional activation of the cardiac homeobox gene CSX1/NKX2-5 in a B-cell chronic lymphoproliferative disorder
Haematologica 2008 93: 1081-1085. Published online May 19, 2008; doi:10.3324/haematol.12595 [Abstract] [Full Text] [PDF] [Su et al. - Supplementary Appendix]  

This report describes the molecular characterization of the translocation t(5;14)(q35;q11) in a case of B-cell chronic lymphoproliferative disorder. The authors demonstrate the involvement of the TCR gene on chromosome 14 and of the NKX2-5 gene on chromosome 5.

Familial Hemophagocytic Lymphohistiocytosis:

Alessandra Santoro, Sonia Cannella, Antonino Trizzino, Giuseppa Bruno, Carmen De Fusco, Luigi D. Notarangelo, Daniela Pende, Gillian M. Griffiths, Maurizio Aricò

Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3
Haematologica 2008 93: 1086-1090. Published online May 19, 2008; doi:10.3324/haematol.12622 [Abstract] [Full Text] [PDF] [Santoro et al. - Supplementary Appendix]  

This report shows that UNC13D mutations leading to splicing errors are frequent in hemophagocytic lymphohisti-ocytosis type 3. Their detection and identification may be instrumental in the diagnosis of this disease.

Disorders of Hemostasis:

Pilar Casaña, Noelia Cabrera, Ana Rosa Cid, Saturnino Haya, Magdalena Beneyto, Carmen Espinós, Vicente Cortina, Maria Angeles Dasí, Josè Antonio Aznar

Severe and moderate hemophilia A: identification of 38 new genetic alterations
Haematologica 2008 93: 1091-1094. Published online April 9, 2008; doi:10.3324/haematol.12344 [Abstract] [Full Text] [PDF]  

This report describes new mutations of F8 in patients with severe and moderate hemophilia A.

Letters to the Editor:

Thalassemia Syndromes:

Raffaella Origa, Susanna Barella, Giovanni Maria Argiolas, Patrizio Bina, Annalisa Agus, Renzo Galanello

No evidence of cardiac iron in 20 never- or minimally-transfused patients with thalassemia intermedia
Haematologica 2008 93: 1095-1096. Published online May 27, 2008; doi:10.3324/haematol.12484 [Full Text] [PDF]  

Hemoglobinopathies:

Michela Grosso, Ilaria Palumbo, Emanuela Morelli, Stella Puzone, Raffaele Sessa, Paola Izzo

Defective mRNA levels are responsible for a β-thalassemia phenotype associated with Hb Federico II, a novel hemoglobin variant [β-106 (G8) LeuVal]
Haematologica 2008 93: 1096-1098. [Full Text] [PDF]  

Myeloproliferative Disorders:

Ioana Borze, Satu Mustjoki, Eeva Juvonen, Sakari Knuutila

Oligoarray comparative genomic hybridization in polycythemia vera and essential thrombocythemia
Haematologica 2008 93: 1098-1100. [Full Text] [PDF]  

Robert Weinkove, John T. Reilly, Mary Frances McMullin, Natasha J. Curtin, Deepti Radia, Claire N. Harrison

Low-dose thalidomide in myelofibrosis
Haematologica 2008 93: 1100-1101. Published online May 27, 2008; doi:10.3324/haematol.12416 [Full Text] [PDF]  

Chronic Myeloid Leukemia:

Sofia Jönsson, Bob Olsson, Claes Ohlsson, Mattias Lorentzon, Dan Mellström, Hans Wadenvik

Increased cortical bone mineralization in imatinib treated patients with chronic myelogenous leukemia
Haematologica 2008 93: 1101-1103. Published online May 27, 2008; doi:10.3324/haematol.12373 [Full Text] [PDF] [Jonsson et al. - Supplementary Appendix]  

Acute Myeloid Leukemia:

Seiichiro Kobayashi, Yasushi Soda, Yuansong Bai, Arinobu Tojo

RETRACTED: Heterogeneous promoter activity of the telomerase reverse transcriptase gene in individual acute myeloid leukemia cells defined by lentiviral reporter assay
Haematologica 2008 93: 1103-1105. Published online May 27, 2008; doi:10.3324/haematol.12123 [Full Text] [PDF]  

Sabine Teichler, Richard F. Schlenk, Konstantin Strauch, Nicole M. Hagner, Markus Ritter, Andreas Neubauer

Expression of the nuclear oncogene Ski in patients with acute myeloid leukemia treated with all-trans retinoic acid
Haematologica 2008 93: 1105-1107. Published online May 27, 2008; doi:10.3324/haematol.12003 [Full Text] [PDF]  

Malignant Lymphomas:

Gunhild Trøen, Iwona Wlodarska, Abdirashid Warsame, Silvia Hernández Llodrà, Christiane De Wolf-Peeters, Jan Delabie

NOTCH2 mutations in marginal zone lymphoma
Haematologica 2008 93: 1107-1109. Published online May 27, 2008; doi:10.3324/haematol.11635 [Full Text] [PDF]  

Monoclonal Gammopathies:

Stéphanie Poulain, Isabelle Dervite, Xavier Leleu, Valérie Coiteux, Patrick Duthilleul, Pierre Morel

The IL6(-174G/C) polymorphism is a prognostic factor for survival after treatment initiation in Waldenström macroglobulinemia patients aged 65 years or less
Haematologica 2008 93: 1109-1111. Published online May 27, 2008; doi:10.3324/haematol.12530 [Full Text] [PDF]  

Chronic Lymphocytic Leukemia:

Thorsten Zenz, Sonja Häbe, Axel Benner, Dirk Kienle, Hartmut Döhner, Stephan Stilgenbauer

The MDM2 –309 T/G promoter single nucleotide polymorphism does not alter disease characteristics in chronic lymphocytic leukemia
Haematologica 2008 93: 1111-1113. Published online May 27, 2008; doi:10.3324/haematol.12738 [Full Text] [PDF] [Zenz et al. - Supplementary Appendix]  

Platelets:

Giovanni Emilia, Mario Luppi, Monica Morselli, Fabio Forghieri, Leonardo Potenza, Giuseppe Torelli

A possible role for low-dose cyclosporine in refractory immune thrombocytopenic purpura
Haematologica 2008 93: 1113-1115. Published online May 27, 2008; doi:10.3324/haematol.12741 [Full Text] [PDF]  

Thrombosis:

Montserrat Borrell, Isabel Tirado, José Mateo, Artur Oliver, Amparo Santamaría, Jordi Fontcuberta

IgM anti-protein S antibodies as a risk factor for venous thrombosis
Haematologica 2008 93: 1115-1117. Published online May 27, 2008; doi:10.3324/haematol.12575 [Full Text] [PDF]  

Karine Lacut, Jantien van der Maaten, Grégoire Le Gal, Géraldine Cornily, Dominique Mottier, Emmanuel Oger

Antiplatelet drugs and risk of venous thromboembolism: results from the EDITH case-control study
Haematologica 2008 93: 1117-1118. [Full Text] [PDF]  

Gaucher Disease:

Maaike de Fost, Carel J.M. van Noesel, Johannes M.F.G. Aerts, Mario Maas, Ruud G. Pöll, Carla E.M. Hollak

Persistent bone disease in adult type 1 Gaucher disease despite increasing doses of enzyme replacement therapy
Haematologica 2008 93: 1119-1120. Published online June 2, 2008; doi:10.3324/haematol.12651 [Full Text] [PDF]  

Online Only Articles:

P Bertrand, C Maingonnat, P Ruminy, H Tilly, C Bastard

Comment to: The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement. Haematologica 2007; 92:1335-1342
Haematologica 2008 93: e53. [Full Text] [PDF]  

Hervé Avet-Loiseau

Reply to: [Comment to: The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement. Haematologica 2007; 92:1335-1342
Haematologica 2008 93: e54. [Full Text] [PDF]  

Giuseppe Lippi, Massimo Franchini, Bengt Kayser

Comment to: Recombinant erythropoietin found in seized blood bags from sportsmen. Haematologica 2008;93:313–4
Haematologica 2008 93: e55. [Full Text] [PDF]  

Joaquim Mallorqui, Jordi Segura, Carme de Bolòs, Ricardo Gutierrez-Gallegom, José A. Pascual

Reply to: [Comment to: Recombinant erythropoietin found in seized blood bags from sportsmen. Haematologica 2008;93:313-4
Haematologica 2008 93: e56. [Full Text] [PDF]  

Ellen van der Spek, René van der Griend

Comment to: Secondary malignancies after treatment for indolent non-Hodgkin’s lymphoma: a 16-year follow-up study. Haematologica 2008; 93:398-403
Haematologica 2008 93: e57. [Full Text] [PDF]  

S. Sacchi

Reply to: [Comment to: Secondary malignancies after treatment for indolent non-Hodgkin’s lymphoma: a 16-year follow-up study. Haematologica 2008; 93:398-403
Haematologica 2008 93: e58. [Full Text] [PDF]  

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