Editorials and Perspectives:

Tea Soon Park, Elias T. Zambidis

A role for the renin-angiotensin system in hematopoiesis
Haematologica 2009 94: 745-747. [Full Text] [PDF]  

In this perspective article, Drs. Park and Zambidis give a comprehensive overview of the role of the renin-angiotensin system. They highlight that its broad function goes beyond the well-characterized activities in maintaining cardiovascular homeostasis. See related article on page 857.

Martin Stanulla, André Schrauder

Bridging the gap between the north and south of the world: the case of treatment response in childhood acute lymphoblastic leukemia
Haematologica 2009 94: 748-752. [Full Text] [PDF]  

Minimal residual disease (MRD) analyses provide strong prognostic information and can be used to identify a majority of patients with childhood acute lymphoblastic leukemia at a high risk of relapse. In this perspective article, Drs. Stanulla and Schrauder comprehensively summarize the current knowledge in the field and how simplified MRD analyses can be successfully implemented also in countries with limited economic resources. See related articles on page 781 and 870.

Silvia Deaglio, Fabio Malavasi

Chronic lymphocytic leukemia microenvironment: shifting the balance from apoptosis to proliferation
Haematologica 2009 94: 752-756. [Full Text] [PDF]  

Most information on chronic lymphocytic leukemia has been derived from circulating cells, but, proliferation occurs in tissue sites. Drs. Deaglio and Malavasi examine critical receptor/ligand interactions likely to influence growth or apoptosis in the tissue microenvironment. See related paper on page 790.

Amy E. Geddis

The regulation of proplatelet production
Haematologica 2009 94: 756-759. [Full Text] [PDF]  

The process by which megakaryocytes break down into platelets is slowly becoming clearer. It is now clear that these processes also determine the morphology of the platelets that are formed. Dr Geddis here summarizes recent work using in vitro and in vivo models, which demonstrate how factors within the megakaryocyte and their interactions with the marrow environment give rise to normal and abnormal platelets. See related article on page 800.

James N. George

Definition, diagnosis and treatment of immune thrombocytopenic purpura
Haematologica 2009 94: 759-762. [Full Text] [PDF]  

Novel drugs have recently been approved for the treatment of immune thrombocytopenic purpura. In this perspective article, Dr. George examines definition, diagnosis and treatment of this condition. See related article on page 850.

Joseph Emmerich

1-antitrypsin and the maintenance of hemostatic balance
Haematologica 2009 94: 762-763. [Full Text] [PDF]  

Although antitrypsin usually plays only minor role in hemostasis, a single point mutation can convert it into a potent inhibitor of thrombin and produce an associated bleeding tendency. In this perspective article, Dr. Emmerich compares the phenotype and laboratory findings in the three available reports of this rare phenomenon. See related article on page 881.

Paying for open access
Haematologica 2009 94: 764. [Full Text] [PDF]  

Haematologica is owned by a non-profit organization, the Ferrata Storti Foundation, and serves the scientific community with strict adherence to the principles of open access publishing. A number of recent initiatives aimed at improving the journal further have had a significant impact on production costs. To continue to provide open access, the journal now needs to share these high costs of publication with authors. Therefore, authors are now required to pay page charges.

Original Article:

Guillemette Ramey, Jean-Christophe Deschemin, Sophie Vaulont

Cross-talk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holotransferrin in primary mouse hepatocytes
Haematologica 2009 94: 765-772. Published online May 19, 2009; doi:10.3324/haematol.2008.003541 [Abstract] [Full Text] [PDF]  

The circulating hormone hepcidin plays a central role in iron homeostasis. The findings of this study show that transcriptional activation of hepcidin by holotransferrin occurs in primary mouse hepatocytes through both BMP/HJV and TFR2/ERK pathways.

Pavle Matak, Timothy B. Chaston, Bomee Chung, Surjit Kaila Srai, Andrew T. McKie, Paul A. Sharp

Activated macrophages induce hepcidin expression in HuH7 hepatoma cells
Haematologica 2009 94: 773-780. Published online May 19, 2009; doi:10.3324/haematol.2008.003400 [Abstract] [Full Text] [PDF]  

Macrophage-released cytokines are relevant in modulating hepcidin expression. The findings of this study suggest that the interleukin-1b and bone morphogenetic protein signaling pathways are central to the regulation of hepcidin expression by macrophages.

Carlos A. Scrideli, Juliana G. Assumpção, Mônica A. Ganazza, Marcela Araújo, Silvia R. Toledo, Maria Lúcia M. Lee, Elisabete Delbuono, Antonio S. Petrilli, Rosane P. Queiróz, Andrea Biondi, Marcos B. Viana, José A. Yunes, Silvia R. Brandalise, Luiz G. Tone

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups
Haematologica 2009 94: 781-789. [Abstract] [Full Text] [PDF]  

This paper describes a simplified PCR strategy for minimal residual disease (MRD) monitoring in children with acute lymphoblastic leukemia. Since this method is cheaper and simpler than standard methods, it may be particularly suitable for countries with limited economic resources. See related perspective article on page 748.

Basile Stamatopoulos, Benjamin Haibe-Kains, Carole Equeter, Nathalie Meuleman, Anne Sorée, Cécile De Bruyn, Delphine Hanosset, Dominique Bron, Philippe Martiat, Laurence Lagneaux

Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA
Haematologica 2009 94: 790-799. Published online April 18, 2009; doi:10.3324/haematol.2008.002626 [Abstract] [Full Text] [PDF] [Stamatopoulos et al. Supplementary Appendix]  

ZAP70 is a strong indicator of poor prognosis in chronic lymphocytic leukemia. In this study, using gene expression profiles associated with ZAP70 expression, the importance of microenvironmental interaction for tumor behavior is revealed. See related perspective article on page 752.

Catherine Strassel, Anita Eckly, Catherine Léon, Claire Petitjean, Monique Freund, Jean-Pierre Cazenave, Christian Gachet, François Lanza

Intrinsic impaired proplatelet formation and microtubule coil assembly of megakaryocytes in a mouse model of Bernard-Soulier syndrome
Haematologica 2009 94: 800-810. Published online April 18, 2009; doi:10.3324/haematol.2008.001032 [Abstract] [Full Text] [PDF] [Strassel et al. Supplementary Appendix]  

Bernard-Soulier syndrome is caused by a deficiency of the platelet surface glycoprotein Ib-IX-V complex resulting in a severe platelet function defect. However this is compounded by a reduction in platelet numbers and the platelets in the circulation are abnormally large. As for many other platelet disorders, recent evidence and findings of this study suggest that the defective morphology has its origins in megakaryocyte function. See related perspective article on page 756.

Mirjam E. Meltzer, Carine J.M. Doggen, Philip G. de Groot, Joost C.M. Meijers, Frits R. Rosendaal, Ton Lisman

Low thrombin activatable fibrinolysis inhibitor activity levels are associated with an increased risk of a first myocardial infarction in men
Haematologica 2009 94: 811-818. Published online April 18, 2009; doi:10.3324/haematol.2008.002386 [Abstract] [Full Text] [PDF]  

Case control studies can be useful ways of investigating mechanisms of disease but demonstrate associations rather than proving causes. Thus it should not be surprising that the results are sometimes not intuitively obvious or run counter to what is expected. In this report from a large case-control study this is exactly what has occurred. Corresponding genetic analyses are unable to resolve the problem, but the complexity of the coagulation system and its relationship with inflammation is able to provide alternative explanations.

Fabrizio Semeraro, Concetta T. Ammollo, Nicola Semeraro, Mario Colucci

Tissue factor-expressing monocytes inhibit fibrinolysis through a TAFI-mediated mechanism, and make clots resistant to heparins
Haematologica 2009 94: 819-826. Published online April 18, 2009; doi:10.3324/haematol.2008.000042 [Abstract] [Full Text] [PDF] [Semeraro et al. - Supplementary appendix]  

It is often noted that the activation of the fibrinolytic system begins as the clot is formed, but it is also true that antifibrinolytic mechanisms are activated at the same time and both depend on the generation of thrombin. In this paper, the authors show that the increased thrombin generation driven by monocyte-associated tissue factor activates TAFI and thus make the clot more resistant to fibrinolysis.

Federico Moscardó, Jaime Sanz, Leonor Senent, Susana Cantero, Javier de la Rubia, Pau Montesinos, Dolores Planelles, Ignacio Lorenzo, Jose Cervera, Javier Palau, Miguel A. Sanz, Guillermo F. Sanz

Impact of hematopoietic chimerism at day +14 on engraftment after unrelated donor umbilical cord blood transplantation for hematologic malignancies
Haematologica 2009 94: 827-832. [Abstract] [Full Text] [PDF]  

Primary graft failure remains a substantial setback of umbilical cord blood transplantation (CBT). The results of this study emphasize that the extent of donor chimerism very early post-transplant is predictive of hematopoietic engraftment following single-unit CBT in adult patients suffering from malignant hematologic disease.

Antonio Piralla, Elena Percivalle, Alessandra Di Cesare-Merlone, Franco Locatelli, Giuseppe Gerna

Multicluster nosocomial outbreak of parainfluenza virus type 3 infection in a pediatric oncohematology unit: a phylogenetic study
Haematologica 2009 94: 833-839. Published online April 18, 2009; doi:10.3324/haematol.2008.003319 [Abstract] [Full Text] [PDF]  

Human parainfluenza virus type 3 (hPIV-3) has been reported to cause nosocomial outbreaks of respiratory infection, in particular among hematopoietic stem cell transplant. The results of the present study indicate that a nosocomial outbreak of hPIV-3 infection occurred among patients followed in an Oncohematology Unit over a period of about 15 weeks during the fall season.

Review Article:

Andrew J. Ramsay, John D. Hooper, Alicia R. Folgueras, Gloria Velasco, Carlos López-Otín

Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis
Haematologica 2009 94: 840-849. Published online April 18, 2009; doi:10.3324/haematol.2008.001867 [Abstract] [Full Text] [PDF]  

The family of membrane anchored serine proteases is increasingly being acknowledged as having critical physiological functions, exemplified recently by the discovery of the iron regulatory role of matriptase-2. This protease, encoded by TMRPSS6, has a specific role in hepcidin inhibition and iron absorption. In this review article, the authors discuss our current knowledge on this new and exciting issue.

Decision Making and Problem Solving:

Donald M. Arnold, Ashley Bernotas, Ishac Nazi, Roberto Stasi, Masataka Kuwana, Yang Liu, John G. Kelton, Mark A. Crowther

Platelet count response to H. pylori treatment in patients with immune thrombocytopenic purpura with and without H. pylori infection: a systematic review
Haematologica 2009 94: 850-856. [Abstract] [Full Text] [PDF]  

Eradication of H. pylori improves thrombocytopenia in some patients with immune thrombocytopenic purpura by mechanisms that remain obscure. To determine the independent effect of H. pylori eradication therapy on platelet count response, the authors performed a systematic review of all studies reporting treatment responses compared to H. pylori-negative controls. The findings strengthen the causal association between H. pylori infection and immune thrombocytopenia in some patients. See related perspective article on page 759.

Brief Reports:

Silvia Heringer-Walther, Klaus Eckert, Sarah-Mai Schumacher, Lutz Uharek, Annika Wulf-Goldenberg, Florian Gembardt, Iduna Fichtner, Heinz-Peter Schultheiss, Kathy Rodgers, Thomas Walther

Angiotensin-(1–7) stimulates hematopoietic progenitor cells in vitro and in vivo
Haematologica 2009 94: 857-860. Published online April 18, 2009; doi:10.3324/haematol.2008.000034 [Abstract] [Full Text] [PDF]  

This study demonstrates that the angiotensin II metabolite Ang-(1-7) stimulates the proliferation of hematopoietic progenitor cells and promotes their engraftment in a xenograft model, suggesting that the renin-angiotensin system is a regulator of blood cell formation. See related perspective article on page 745.

Jamshid Sorouri Khorashad, Simon Wagner, Liat Greener, David Marin, Alistair Reid, Dragana Milojkovic, Hetal Patel, Shaun Willimott, Katy Rezvani, Gareth Gerrard, Sandra Loaiza, John Davis, John Goldman, Junia Melo, Jane Apperley, Letizia Foroni

The level of BCR-ABL1 kinase activity before treatment does not identify chronic myeloid leukemia patients who fail to achieve a complete cytogenetic response on imatinib
Haematologica 2009 94: 861-864. Published online April 18, 2009; doi:10.3324/haematol.2008.003715 [Abstract] [Full Text] [PDF]  

This study investigated the in vitro inhibition of Crkl phosphorylation by imatinib in CD34+ cells from patients with chronic myeloid leukemia, and showed that it does not correlate with the cytogenetic response, possibly indicating that BCR-ABL1-independent resistance mechanisms exist.

François Girodon, Gilles Bonicelli, Céline Schaeffer, Morgane Mounier, Serge Carillo, Ingrid Lafon, Paule Marie Carli, Inès Janoray, Emmanuelle Ferrant, Marc Maynadié

Significant increase in the apparent incidence of essential thrombocythemia related to new WHO diagnostic criteria: a population-based study
Haematologica 2009 94: 865-869. Published online April 18, 2009; doi:10.3324/haematol.2008.004234 [Abstract] [Full Text] [PDF]  

The findings of this study confirm the relevance of the new WHO diagnostic criteria in allowing earlier diagnosis of essential thrombocythemia.

Julie Irving, Jenny Jesson, Paul Virgo, Marian Case, Lynne Minto, Lisa Eyre, Nigel Noel, Ulrika Johansson, Marion Macey, Linda Knotts, Margaret Helliwell, Paul Davies, Liam Whitby, David Barnett, Jeremy Hancock, Nick Goulden, Sarah Lawson on behalf of the UKALL Flow MRD group and UK MRD steering group

Establishment and validation of a standard protocol for the detection of minimal residual disease in B lineage childhood acute lymphoblastic leukemia by flow cytometry in a multi-center setting;
Haematologica 2009 94: 870-874. Published online April 18, 2009; doi:10.3324/haematol.2008.000414 [Abstract] [Full Text] [PDF] [Irving et al. Supplementary Appendix]  

Flow cytometry to detect minimal residual disease is a sensitive and specific means to detect impending relapse in B lineage acute lymphoblastic leukemia (ALL). However as with all relatively sophisticated procedures assurance is needed that the methodology is widely applicable, and reproducible in different laboratories. In this paper, the UK ALL Flow MRD Group and the UK MRD steering group describe a four color flow protocol that was applicable to most patients and showed similarly high levels of concordance both between different laboratories and with MRD as detected molecularly. See related perspective article on page 748.

Mark Bower, Martin Fisher, Teresa Hill, Iain Reeves, John Walsh, Chloe Orkin, Andrew N. Phillips, Loveleen Bansi, Richard Gilson, Philippa Easterbrook, Margaret Johnson, Brian Gazzard, Clifford Leen, Deenan Pillay, Achim Schwenk, Jane Anderson, Kholoud Porter, Mark Gompels, Caroline A. Sabin, for the UK CHIC Steering Committee

CD4 counts and the risk of systemic non-Hodgkin’s lymphoma in individuals with HIV in the UK
Haematologica 2009 94: 875-880. Published online March 31, 2009; doi:10.3324/haematol.2008.002691 [Abstract] [Full Text] [PDF] [Bower et al. - Supplementary Appendix]  

This very large HIV-positive cohort study examines a number of variables that predispose to the development of lymphoma in the HAART era. Despite a declining incidence of lymphoma, the authors define a close relationship between latest CD4 count and lymphoma risk, and thus advocate early initiation of HAART and more frequent HIV monitoring.

Baolai Hua, Liankai Fan, Yan Liang, Yongqiang Zhao, Edward G.D. Tuddenham

₁-antitrypsin Pittsburgh in a family with bleeding tendency
Haematologica 2009 94: 881-884. [Abstract] [Full Text] [PDF]  

A rare but naturally occurring mutation turns alpha1 antitrypsin into a potent antithrombin resulting in a bleeding tendency. This extremely rare phenomenon has been described before, but this additional family provides an interesting insight into the balance of coagulation.

Letter to the Editor:

Joyce J.C. Kroot, Coby M.M. Laarakkers, Erwin H.J.M. Kemna, Bart J. Biemond, Dorine W. Swinkels

Regulation of serum hepcidin levels in sickle cell disease
Haematologica 2009 94: 885-887. [Full Text] [PDF]  

Massimo Gentile, Giovanna Cutrona, Antonino Neri, Stefano Molica, Manlio Ferrarini, Fortunato Morabito

Predictive value of β2-microglobulin (β2-m) levels in chronic lymphocytic leukemia since Binet A stages
Haematologica 2009 94: 887-888. [Full Text] [PDF]  

Françoise Lasne, Laurent Martin, Jean Antoine Martin, Jacques de Ceaurriz

Detection of continuous erythropoietin receptor activator in blood and urine in anti-doping control
Haematologica 2009 94: 888-890. [Full Text] [PDF]  

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