Editorials and Perspectives:

Marie C. Béné

Biphenotypic, bilineal, ambiguous or mixed lineage: strange leukemias!
Haematologica 2009 94: 891-893. [Full Text] [PDF]  

The criteria for "biphenotypic acute leukemia" have changed with improvements in the ability to distinguish blast cells of different lineages. In her perspective on the paper by Xu et al (page 918) Dr. Béné reviews these changes, proceeding up to the most recent WHO classification. See also related review article on page 984.

Daphne de Jong

Novel lymphoid neoplasms – the borderland between diffuse large B-cell lymphoma and Burkitt’s lymphoma
Haematologica 2009 94: 894-896. [Full Text] [PDF]  

The recent update of the WHO classification of tumors of the lymphoid tissue has recognized a category with overlapping features between Burkitt lymphoma and diffuse large B-cell lymphoma. In this perspective article, Dr. de Jong reviews the conceptual basis and practical impact of this diagnosis. See related paper on page 935.

Brunangelo Falini, Maria Paola Martelli

Anaplastic large cell lymphoma: changes in the World Health Organization classification and perspectives for targeted therapy
Haematologica 2009 94: 897-900. [Full Text] [PDF]  

The accompanying perspective by Drs. Falini and Martelli provides a clear description of the current WHO classification with a focus on the distinction between ALK-positive anaplastic large cell lymphoma ALCL and ALK-negative disease. Additionally, they provide a rationale for potential new targets for therapy including flavopiridol. See related paper on page 944.

Original Article:

Hematopoietic Stem Cells:

Christian R. Geest, Fried J. Zwartkruis, Edo Vellenga, Paul J. Coffer, Miranda Buitenhuis

Mammalian target of rapamycin activity is required for expansion of CD34⁺ hematopoietic progenitor cells
Haematologica 2009 94: 901-910. Published online June 16, 2009; doi:10.3324/haematol.13766 [Abstract] [Full Text] [PDF]  

The protein kinase mammalian target of rapamycin (mTOR) plays an essential role in the control of protein synthesis. In this paper, Geest and colleagues show that mTOR inhibition by rapamycin reduces the expansion of committed myeloid progenitors, but leaves the more primitive hematopoietic compartment unaffected.

Myeloproliferative Neoplasms:

Marijke C. Trappenburg, Muriel van Schilfgaarde, Marina Marchetti, Henri M. Spronk, Hugo ten Cate, Anja Leyte, Wim E. Terpstra, Anna Falanga

Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia
Haematologica 2009 94: 911-918. Published online June 8, 2009; doi:10.3324/haematol.13774 [Abstract] [Full Text] [PDF]  

Essential thrombocythemia is a myeloproliferative neoplasm characterized by an increased risk of both arterial and venous thrombosis. The findings of this study show that patients with this disorder have elevated levels of platelet-and endothelium-derived microparticles, which may support thrombin generation and play a role in the pathophysiology of thromboembolic complications.

Acute Leukemia:

Xiao-Qian Xu, Jian-Min Wang, Shu-Qing Lü, Li Chen, Jian-Min Yang, Wei-Ping Zhang, Xian-Min Song, Jun Hou, Xiong Ni, Hui-Ying Qiu

Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population
Haematologica 2009 94: 919-927. Published online May 19, 2009; doi:10.3324/haematol.2008.003202 [Abstract] [Full Text] [PDF]  

Biphenotypic acute leukemia is rare, necessitating large series to provide information on prognosis. In this paper Xu and colleagues review Chinese experience with this conditions. The findings of this study indicate that the prognosis of biphenotypic acute leukemia patients is poor when compared with de novo acute myeloid leukemia or acute lymphoblastic leukemia. See related perspective article on page 891 and related review article on page 984.

Patries M. Herst, Joanne E. Davis, Paul Neeson, Michael V. Berridge, David S. Ritchie

The anti-cancer drug, phenoxodiol, kills primary myeloid and lymphoid leukemic blasts and rapidly proliferating T cells
Haematologica 2009 94: 928-934. Published online June 16, 2009; doi:10.3324/haematol.2008.003996 [Abstract] [Full Text] [PDF]  

The plasma electron transport system is a relatively newly-discovered potential target for anti-leukemia drugs. In this paper Herst and coworkers describe the effects of phenoxodiol, an inhibitor of this pathway on leukemia cell lines and primary as well as on resting and activated T cells. The ability of phenoxodiol to kill rapidly proliferating lymphocytes might make this drug a promising candidate for the treatment of pathologically-activated lymphocytes.

Malignant Lymphomas:

Naoto Tomita, Mami Tokunaka, Naoya Nakamura, Kengo Takeuchi, Junki Koike, Shigeki Motomura, Ko Miyamoto, Ako Kikuchi, Rie Hyo, Yoshihiro Yakushijin, Yasufumi Masaki, Soichiro Fujii, Takamasa Hayashi, Yoshiaki Ishigatsubo, Ikuo Miura

Clinicopathological features of lymphoma/leukemia patients carrying both BCL2 and MYC translocations
Haematologica 2009 94: 935-943. Published online June 16, 2009; doi:10.3324/haematol.2008.005355 [Abstract] [Full Text] [PDF]  

Malignant lymphoid neoplasms carrying both MYC and BCL2 translocations ("double hit" lymphomas) are uncommon and have a very aggressive clinical behavior. This thorough study by Tomita and coworkers characterizes a large series of these patients recognizing their poor outcome and frequent extranodal and CNS involvement. See related perspective article on page 894.

Paolo Bonvini, Elisa Zorzi, Lara Mussolin, Giovanni Monaco, Martina Pigazzi, Giuseppe Basso, Angelo Rosolen

The effect of the cyclin-dependent kinase inhibitor flavopiridol on anaplastic large cell lymphoma cells and relationship with NPM-ALK kinase expression and activity
Haematologica 2009 94: 944-955. Published online June 16, 2009; doi:10.3324/haematol.2008.004861 [Abstract] [Full Text] [PDF]  

This study by Bonvini and coworkersd describes in vitro data supporting a role for the CDK inhibitor flavopiridol in the treatment of anaplastic large cell lymphoma. Moreover, their studies establish a link between ALK over-expression and flavopiridol, as inhibition of ALK activity sensitizes the cells to flavopiridol-induced cell death. See related perspective article on page 897.

Stem Cell Transplantation:

Katie Matthews, ZiYi Lim, Behdad Afzali, Laurence Pearce, Atiyeh Abdallah, Shahram Kordasti, Antonio Pagliuca, Giovanna Lombardi, J. Alejandro Madrigal, Ghulam J. Mufti, Linda D. Barber

Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab
Haematologica 2009 94: 956-966. Published online June 2, 2009; doi:10.3324/haematol.2008.003103 [Abstract] [Full Text] [PDF]  

Graft-versus-host disease (GVHD) remains the downside of the graft-versus-leukemia effect following allogeneic stem cell transplantation. This investigation of 25 patients with myeloid malignancies treated with reduced intensity conditioning and with GVHD prophylaxis, has focused on cell populations and their correlation with outcome. Interesting imbalances of effector and regulatory CD4+ T cells were detected, which, if confirmed in larger cohorts, should provide insight into how the immunological storms accompanying allogeneic stem cell transplantation can be harnessed and weathered.

Cell Therapy and Immunotherapy:

Davide Bagnara, Adalberto Ibatici, Mirko Corselli, Nadia Sessarego, Claudya Tenca, Amleto De Santanna, Andrea Mazzarello, Antonio Daga, Renzo Corvò, Giulio De Rossi, Francesco Frassoni, Ermanno Ciccone, Franco Fais

Adoptive immunotherapy mediated by ex vivo expanded natural killer T cells against CD1d-expressing lymphoid neoplasms
Haematologica 2009 94: 967-974. Published online May 19, 2009; doi:10.3324/haematol.2008.001339 [Abstract] [Full Text] [PDF] [Bagnara et al. - Supplementary Appendix]  

Therapy of tumors by injection of T cells is gaining attention, although technical problems remain. This pre-clinical study investigates the potential of NKT cells, readily expanded in vitro and having a relatively wide specificity, determined by target expression of CD1d. This is attractive for lymphoid tumors and the data show attack on a xenograft in vivo in the presence of the CD1d-binding alpha-galactosylceramide. While clinical application is not immediate, the model allows useful dissection of an intriguing concept.

Belén Blanco, José A. Pérez-Simón, Luis I. Sánchez-Abarca, Teresa Caballero-Velazquez, Silvia Gutierrez-Cossío, Pilar Hernández-Campo, María Díez-Campelo, Carmen Herrero-Sanchez, Concepción Rodriguez-Serrano, Carlos Santamaría, Fermín M. Sánchez-Guijo, Consuelo del Cañizo, Jesús F. San Miguel

Treatment with bortezomib of human CD4⁺ T cells preserves natural regulatory T cells and allows the emergence of a distinct suppressor T-cell population
Haematologica 2009 94: 975-983. Published online June 8, 2009; doi:10.3324/haematol.2008.005017 [Abstract] [Full Text] [PDF]  

In vitro depletion of alloreactive T cells using the proteasome inhibitor bortezomib is a promising approach to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. The findings of this study strengthen the idea of using bortezomib in the prevention of GVHD, not only because of its selective cytotoxic effect on activated T cells, but also due to its ability to preserve and/or generate regulatory T cells.

Review Article:

Acute Leukemia:

Robert K. Slany

The molecular biology of mixed lineage leukemia
Haematologica 2009 94: 984-993. Published online June 16, 2009; doi:10.3324/haematol.2008.002436 [Abstract] [Full Text] [PDF]  

Mixed-lineage-leukemia is an aggressive leukemia that predominantly occurs in pediatric patients and is characterized by the expression of fusion genes involving the histone methyltransferase MLL and a variety of fusion partners. It is now clear that MLL fusion partners can activate transcription by two different mechanisms, which are discussed in this review article. Insights in these functions may open new avenues for rational drug development. See related papers on page 891 and 918.

Decision Making and Problem Solving:

Blood Cell Morphology:

Jean E. Goasguen, John M. Bennett, Barbara J. Bain, Teresa Vallespi, Richard Brunning, Ghulam J. Mufti for the International Working Group on Morphology of Myelodysplastic Syndrome (IWGM-MDS)

Morphological evaluation of monocytes and their precursors
Haematologica 2009 94: 994-997. Published online June 16, 2009; doi:10.3324/haematol.2008.005421 [Abstract] [Full Text] [PDF]  

This study establishes morphological definitions so that monocytes, including immature monocytes, can be reliably separated from the spectrum of monocyte precursors.

Infectious Disorders:

Panayiotis D. Ziakas, Petros Karsaliakos, Eleftherios Mylonakis

Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance
Haematologica 2009 94: 998-1005. Published online May 19, 2009; doi:10.3324/haematol.2009.005819 [Abstract] [Full Text] [PDF] [Ziakas et al. - Supplementary Appendix]  

Previous observations indicate that a lamividune-prophylaxis strategy results in a decrease of hepatitis B virus (HBV) reactivation rates. This report evaluates the benefits from this strategy among lymphoma patients. The findings of this study indicate that extended anti-HBV prophylaxis can improve survival rates by 2.4% in HBsAg-positive lymphoma patients receiving chemotherapy.

Brief Reports:

Sickle Cell Disease:

Melanie J. Marshall, Romola S. Bucks, Alexandra M. Hogan, Ian R. Hambleton, Susan E. Height, Moira C. Dick, Fenella J. Kirkham, David C. Rees

Auto-adjusting positive airway pressure in children with sickle cell anemia: results of a phase I randomized controlled trial
Haematologica 2009 94: 1006-1010. [Abstract] [Full Text] [PDF]  

Sleep related breathing disorders and especially low nocturnal oxygen saturation may favor complications of sickle cell disease (SCD) In this phase I trial, autoadjusting continuous positive airway pressure (CPAP) was shown to be a feasible and safe therapy for SCD children. Sleep breathing disorders were improved, and there was evidence of a trend towards reduction of diurnal pain.

Bone Marrow Failure:

Michael D. Milsom, Andrew W. Lee, Yi Zheng, Jose A. Cancelas

Fanca^–/– hematopoietic stem cells demonstrate a mobilization defect which can be overcome by administration of the Rac inhibitor NSC23766
Haematologica 2009 94: 1011-1015. Published online June 2, 2009; doi:10.3324/haematol.2008.004077 [Abstract] [Full Text] [PDF]  

In Fanconi anemia, gene and cell therapy trials using hematopoietic stem cells and progenitors have been hampered by poor mobilization of these stem cells to peripheral blood in response to G-CSF. This study shows that that targeting Rac signaling may enhance G-CSF-induced hematopoietic stem cell mobilization in this bone marrow failure syndrome.

Acute Lymphoblastic Leukemia:

Miroslav Djokic, Elisabet Björklund, Elisabeth Blennow, Joanna Mazur, Stefan Söderhäll, Anna Porwit

Overexpression of CD123 correlates with the hyperdiploid genotype in acute lymphoblastic leukemia
Haematologica 2009 94: 1016-1019. Published online May 19, 2009; doi:10.3324/haematol.2008.000299 [Abstract] [Full Text] [PDF]  

This study on patients with acute lymphoblastic leukemia (ALL) shows that overexpression of CD123 is an aberrant phenotype present in a subset of precursor-B ALL with hyperdiploid genotype, and represents an additional marker of good prognosis in pediatric precursor-B ALL.

Malignant Lymphomas:

Inga Nagel, Takashi Akasaka, Wolfram Klapper, Stefan Gesk, Sebastian Böttcher, Matthias Ritgen, Lana Harder, Michael Kneba, Martin J.S. Dyer, Reiner Siebert

Identification of the gene encoding cyclin E1 (CCNE1) as a novel IGH translocation partner in t(14;19)(q32;q12) in diffuse large B-cell lymphoma
Haematologica 2009 94: 1020-1023. Published online May 19, 2009; doi:10.3324/haematol.2008.000968 [Abstract] [Full Text] [PDF]  

Cyclin D family members are known to be ectopically expressed in B-cell lymphomas due to their involvement in chromosomal translocations with the immunoglobulin loci (IGH). This study identified the gene encoding cyclin E1 (CCNE1) as a novel translocation partner of IGH in diffuse large B-cell lymphoma. These observations suggest that cyclin E1 may act as a novel oncogene in B-cell lymphomagenesis.

Multiple Myeloma:

Laura Chiecchio, Gian Paolo Dagrada, Rebecca K.M. Protheroe, David M. Stockley, Alastair G. Smith, Kim H. Orchard, Nicholas C.P. Cross, Christine J. Harrison, Fiona M. Ross on behalf of the UK Myeloma Forum

Loss of 1p and rearrangement of MYC are associated with progression of smouldering myeloma to myeloma: sequential analysis of a single case
Haematologica 2009 94: 1024-1028. Published online May 19, 2009; doi:10.3324/haematol.2008.004440 [Abstract] [Full Text] [PDF]  

This case report suggests that loss of 1p and rearrangement of MYC are associated with progression of smoldering myeloma to to multiple myeloma.

Amyloidosis:

Saulius Girnius, David C. Seldin, Martha Skinner, Kathleen T. Finn, Karen Quillen, Gheorghe Doros, Vaishali Sanchorawala

Hepatic response after high-dose melphalan and stem cell transplantation in patients with AL amyloidosis associated liver disease
Haematologica 2009 94: 1029-1032. Published online May 19, 2009; doi:10.3324/haematol.2008.001925 [Abstract] [Full Text] [PDF]  

In patients with AL amyloidosis and liver involvement, treatment with high-dose melphalan chemotherapy and autologous peripheral blood stem cell transplantation resulted in 61% overall survival at 5 years. Moreover, the transplant-related mortality (13%) was similar to that of patients with AL amyloidosis without associated liver disease.

Letters to the Editor:

Acute Myeloid Leukemia:

Brian V. Balgobind, C. Michel Zwaan, Claus Meyer, Rolf Marschalek, Rob Pieters, H. Berna Beverloo, Marry M. Van den Heuvel-Eibrink

NRIP3: a novel translocation partner of MLL detected in a pediatric acute myeloid leukemia with complex chromosome 11 rearrangements
Haematologica 2009 94: 1033. Published online May 19, 2009; doi:10.3324/haematol.2008.004564 [Full Text] [PDF]  

Acute Lymphoblastic Leukemia:

Jasmine Healy, Marie-Helene Roy-Gagnon, Daniel Sinnett

No evidence for association between TGFB1 promoter SNPs and the risk of childhood pre-B acute lymphoblastic leukemia among French Canadians
Haematologica 2009 94: 1034-1035. Published online June 2, 2009; doi:10.3324/haematol.2009.005991 [Full Text] [PDF]  

Malignant Lymphomas:

Anna Gazzola, Clara Bertuzzi, Claudio Agostinelli, Simona Righi, Stefano A. Pileri, Pier Paolo Piccaluga

Physiological PTEN expression in peripheral T-cell lymphoma not otherwise specified
Haematologica 2009 94: 1036-1037. Published online June 8, 2009; doi:10.3324/haematol.2009.006718 [Full Text] [PDF]  

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