Abstract:
OBJECTIVE:To characterize the underlying genetic and molecular defects in a consanguineous family with lifelong blood disorder manifested with thrombocytopenia (low platelets count) and anemia. METHODS:Genetic linkage analysis, exome sequencing, and functional genomics were carried out to identify and characterize the defective gene. RESULTS:We identified a novel truncation mutation (p.C108*) in chromosome 6 open reading frame 25 (C6orf25) gene in this family. We also showed the p.C108* mutation was responsible for destabilizing the encoded truncated G6B protein. Unlike the truncated form, wild-type G6B expression resulted in enhanced K562 differentiation into megakaryocytes and erythrocytes. C6orf25, also known as G6B, is an effector protein for the key hematopoiesis regulators, Src homology region 2 domain-containing phosphatases SHP-1 and SHP-2. CONCLUSION:G6B seems to act through an autosomal recessive mode of disease transmission in this family and regarded as the gene responsible for the observed hematological disorder. This inference is well supported further by in vivo evidence where similar outcomes were reported from G6b-/- and SHP1/2 DKO mouse models.
journal_name
Eur J Haematoljournal_title
European journal of haematologyauthors
Melhem M,Abu-Farha M,Antony D,Madhoun AA,Bacchelli C,Alkayal F,AlKhairi I,John S,Alomari M,Beales PL,Alsmadi Odoi
10.1111/ejh.12819subject
Has Abstractpub_date
2017-03-01 00:00:00pages
218-227issue
3eissn
0902-4441issn
1600-0609journal_volume
98pub_type
杂志文章abstract:BACKGROUND:Tumor lysis syndrome (TLS) is a complication that can cause renal failure by precipitation of uric acid (UA) and phosphate crystals in renal tubules. Rasburicase proved to be effective in rapidly reducing UA levels. Costs of rasburicase average up to 4500 euros. To assess if lower doses of rasburicase are ef...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2007.01013.x
更新日期:2008-04-01 00:00:00
abstract::We describe a case of Philadelphia-positive chronic myeloid leukaemia occurring simultaneously with B-cell chronic lymphocytic leukaemia in a 69-yr-old male. Gene probe analysis of DNA from both peripheral blood and bone marrow provided evidence for the independent evolution of 2 clones in this case, with a predominan...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1988.tb00818.x
更新日期:1988-02-01 00:00:00
abstract:OBJECTIVE:The extent of disease in patients with multiple myeloma or related conditions may be difficult to assess. In previous small studies, both FDG-PET (PET) and Tc-99m sestamibi scans (MIBI) have identified sites of occult disease in myeloma. METHODS:We reviewed the results for patients at our institution who hav...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1046/j.0902-4441.2004.00177.x
更新日期:2004-01-01 00:00:00
abstract:OBJECTIVES:To compare the gene expression pattern in children and adults with acute lymphoblastic leukaemia (ALL) in order to improve our understanding of the difference in disease biology and prognosis. METHODS:The gene expression profiles in diagnostic samples from 29 children and 15 adults with ALL were analysed us...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2005.00433.x
更新日期:2005-06-01 00:00:00
abstract:OBJECTIVE:To assess the outcome of the measurement of apoptotic index in myeloma patients treated by conventional chemotherapy and novel drugs with biological mechanism of action, thalidomide and bortezomib. PATIENTS AND METHODS:In a cohort of 189 patients with newly diagnosed multiple myeloma from November 1997 throu...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2009.01321.x
更新日期:2009-12-01 00:00:00
abstract:OBJECTIVE:To correlate different polymorphisms of the beta-globin cluster with fetal hemoglobin (HbF) level in beta-thalassemia and E-beta thalassemia patients. METHODS:Fifteen thalassemia patients, seven with high HbF and not requiring transfusion, eight with lower HbF and requiring transfusion were studied for beta-...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2005.00416.x
更新日期:2005-07-01 00:00:00
abstract::Eighteen patients with malignant lymphoma, 10 non-Hodgkin's and 8 Hodgkin's, were treated with high-dose CVB (cyclophosphamide 4 x 1.5 g/m2, etoposide 4 x 250-400 mg/m2, carmustine 4 x 150-200 mg/m2), followed by autologous peripheral blood stem cells (PBSC, 13 patients) or bone marrow (BM, 5 patients) transplantation...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1993.tb00599.x
更新日期:1993-07-01 00:00:00
abstract::33 patients with advanced refractory multiple myeloma received a combination of vincristine, cyclophosphamide, carmustine, melphalan and steroids (M-2 protocol). 20 of them had failed prior chemotherapy with alkylating agents and the remaining 13 patients had relapsed after a response to these drugs. An objective tumo...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1988.tb00816.x
更新日期:1988-02-01 00:00:00
abstract::In March 1981, a 53-year-old man presented with itching and was diagnosed as having myelofibrosis. There was gradual enlargement of the spleen over the following 5 yr. His spleen had to be removed in February 1986 because of physical discomfort. 3 months post-splenectomy he became polycythaemic. Bone marrow examinatio...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1989.tb00254.x
更新日期:1989-01-01 00:00:00
abstract::Ibrutinib is an oral inhibitor of Bruton tyrosine kinase approved for the treatment of chronic lymphocytic leukaemia, mantle cell lymphoma and refractory Waldenstrom's disease. It increases progression-free survival, overall survival, response rate. The most frequent adverse reactions, are increased risk in of bleedin...
journal_title:European journal of haematology
pub_type:
doi:10.1111/ejh.13290
更新日期:2019-10-01 00:00:00
abstract::Kostmann syndrome (KS) is an inherited hematological disorder characterized by an absolute neutrophil count (ANC) <0.2 x 109/L and life-threatening bacterial infections. Granulocyte-colony stimulating factor (G-CSF) makes it possible to reach an ANC of 1.0 x 109/L and consequently to reduce significantly the occurrenc...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2003.00062.x
更新日期:2003-05-01 00:00:00
abstract::Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1600-0609.1992.tb00030.x
更新日期:1992-08-01 00:00:00
abstract::The incidence of drug-induced skin rashes and related factors were analysed in a retrospective study of 151 patients with acute non-lymphocytic leukaemia (ANLL). 91 (60%) developed a drug-related toxicodermia to one or more drugs during remission, induction and maintenance therapy. The incidence of rashes was mainly c...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1987.tb01168.x
更新日期:1987-03-01 00:00:00
abstract::Little is known about the S100B⁺ lymphocytes, which are unique human peripheral blood lymphocytes (PBL) containing the S100B protein. It has recently been shown that S100B is released from various types of S100B⁺ cells and exhibits varied cytokine-like activities. In this study, we precisely characterized the S100B⁺ l...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12036
更新日期:2013-02-01 00:00:00
abstract::The introduction of novel immunomodulatory drugs (IMiDs) has dramatically improved the survival of patients with multiple myeloma (MM). While it has been shown that patients with specific cytogenetic subtypes, namely t(4;14), have the best outcomes when treated with bortezomib-based regimens, the relationship between ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12192
更新日期:2013-12-01 00:00:00
abstract::This study was conducted in order to assess myocardial and liver iron concentrations (LICs) using serial magnetic resonance imaging (MRI) scans in patients with beta-thalassaemia major, over a 4-yr period, and consequently to compare the effectiveness of different chelation regimens. Fifty children and young adults wi...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.0902-4441.2006.t01-1-EJH3013.x
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVE:Warfarin represents the most commonly prescribed oral anticoagulants, which functions as an antagonist of vitamin K, an essential factor of blood coagulation cascade. Warfarin has a narrow therapeutic index. An insufficient dose can cause failure of antithrombotic effect, and an overdose increases a risk of b...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12348
更新日期:2014-10-01 00:00:00
abstract::Chronic isolated hereditary macrothrombocytopenia (CHMT) is a congenital form of macrothrombocytopenia that seems to be due to defective production secondary to a disturbance in megakaryocyte fragmentation. To better understand the pathogenesis of thrombopoiesis in this hereditary thrombocytopenic disorder, we determi...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2000.90072.x
更新日期:2000-03-01 00:00:00
abstract::Lactoferrin, unlabelled or 125I-labelled by 2 different methods, was given intravenously to rats. Blood, tissue and liver cell radioactivity was measured. Both of the radiolabelled preparations were eliminated by the liver, and some deposited extrahepatically. One preparation formed large aggregates--here 90% of the h...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1998.tb01078.x
更新日期:1998-09-01 00:00:00
abstract::A suitable model for the preclinical study of human platelet production in vivo has not been available. NOD/SCID mice were characterized as representing an efficient engraftment model for human hematopoietic stem cells, which resulted in the production of human platelets. Here, we evaluated in vivo human thrombopoiesi...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2006.00783.x
更新日期:2007-02-01 00:00:00
abstract::The effect of human recombinant interferon alpha 2 (IFN alpha 2) on hairy cells obtained from 16 patients was evaluated. All patients promptly responded to induction of remission with 2 X 10(6) U/m2 interferon alpha 2 b, three times a week, sc. In order to achieve a more detailed insight into the mode of action of int...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1987.tb01449.x
更新日期:1987-11-01 00:00:00
abstract:OBJECTIVES:The aim of this study is to assess the quality of life (QoL) of Chinese adults with idiopathic thrombocytopenic purpura (ITP). METHODS:The Chinese (mainland) version of Medical Outcome Study SF-36 form (SF-36) Health Survey was used to measure health-related QoL of 236 adults with ITP in a cross-sectional s...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2007.00844.x
更新日期:2007-06-01 00:00:00
abstract::Plasma cell leukemia (PCL) is a very aggressive and rare form of malignant monoclonal gammopathy characterized by the presence of plasmocytes in peripheral blood. It is classified as primary PCL occuring 'de novo', or as secondary PCL in patients with relapsed/refractory multiple myeloma. Primary PCL is a distinct cli...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/ejh.12533
更新日期:2015-07-01 00:00:00
abstract::We report a patient with multiple myeloma presenting with a paraspinal plasmacytoma with a marked dissociation between the response obtained in bone marrow (BM) infiltration and that achieved in soft tissue masses. While a complete remission was reached and maintained in BM, extramedullary plasmacytomas were refractor...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2009.01399.x
更新日期:2010-04-01 00:00:00
abstract::This review summarizes present knowledge on porcine platelets in vitro and recent studies on in vivo activation of platelets in the pig. There are certain differences compared to human platelets: Platelet aggregation and secretion cannot be achieved by epinephrine, and the arachidonate pathway seems poorly developed i...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0609.1992.tb00043.x
更新日期:1992-10-01 00:00:00
abstract:OBJECTIVE:Thalidomide is remarkably active in advanced relapsed and refractory multiple myeloma (MM), so that its use has been recently proposed either in newly diagnosed patients or as maintenance treatment after conventional or high-dose therapy. This latter therapeutic approach has risen the concern of side-effects ...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1600-0609.2004.00382.x
更新日期:2005-03-01 00:00:00
abstract::Patients with essential thrombocythemia (ET) often suffer from neurological symptoms (NS) not ever resulting from previous thrombotic cerebral events (TCE). We reported NS occurred in 282 patients, in order to identify the factors influencing ET-related NS in the absence of TCE, and the response to therapy. Overall, 1...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12638
更新日期:2016-06-01 00:00:00
abstract:AIMS:Aim of the study is to investigate diffuse large B-cell lymphoma (DLBCL) for the presence of BCL3 gene rearrangement and protein expression and to correlate these with immunophenotypic subsets of DLBCL. We aimed to investigate the pathogenetic implication of BCL3 in DLBCL. METHODS AND RESULTS:Tissue microarray se...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2011.01684.x
更新日期:2011-12-01 00:00:00
abstract::In recent years, several direct-acting oral anticoagulants (DOAC) have become available for use in Europe and other regions in indications related to prophylaxis and treatment of venous and arterial thromboembolism. They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa, Boehringer Ingelheim) an...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/ejh.12610
更新日期:2015-11-01 00:00:00
abstract::For patients with severe and refractory autoimmune diseases, high-dose chemotherapy and autologous hematopoietic stem cell transplantation has been established as a considerable therapeutic option in recent years. In this retrospective single-center analysis, we assessed the feasibility and efficacy of peripheral bloo...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12686
更新日期:2016-07-01 00:00:00