Abstract:
:The identification of acquired CALR mutations in patients with essential thrombocythaemia (ET) or myelofibrosis (MF) has meant that disease-initiating mutations can now be detected in about 90% of all patients with a myeloproliferative neoplasm (MPN). Here, we show that only those CALR mutations that cause a +1 frameshift, thereby altering the carboxy-terminus of calreticulin, promote cytokine independence in vitro; in-frame deletions were not functional, and are unlikely to be the pathogenetic mutation underlying some MPN cases. Expression of the thrombopoietin receptor, MPL, was also necessary for factor-independence. Although the CALR mutations are considered to occur only in JAK2 V617F-negative cases and in a heterozygous state, progenitor genotyping revealed that this is not always true. Notably, CALR mutation-positive MPNs can be polyclonal: in one case, two distinct CALR mutation-positive subpopulations could be identified; in another, separate populations of JAK2 V617F-positive and CALR-mutated cells were present. Mitotic recombination involving chromosome 19 in a third instance resulted in the emergence of a CALR mutation-homozygous subclone. Collectively, our studies demonstrate that occasional patients with CALR mutation-positive ET or MF carry other MPN-initiating genetic mutations (including JAK2 V617F), acquire "secondary mutations" before or after the CALR mutation, or evolve over time to being CALR mutation-homozygous.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Martin S,Wright CM,Scott LMdoi
10.1111/bjh.14512subject
Has Abstractpub_date
2017-04-01 00:00:00pages
55-66issue
1eissn
0007-1048issn
1365-2141journal_volume
177pub_type
杂志文章abstract::We treated 26 patients with hairy cell leukaemia (HCL) with 2-chlorodeoxyadenosine, including nine with abdominal lymphadenopathy and of whom two had HCL-variant; 18 were previously treated. The overall response in 23 evaluable HCL patients was 100% with 87% complete remission (CR). The CR rate was 57% in patients wit...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2141.1996.5041045.x
更新日期:1996-05-01 00:00:00
abstract::Sickle cell disease (SCD) is increasingly appreciated as an inflammatory condition associated with alterations in immune phenotype and function. In this cross-sectional study we performed a multiparameter analysis of 18 immune markers in 114 paediatric SCD patients divided by treatment group [those receiving hydroxycr...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/bjh.13326
更新日期:2015-05-01 00:00:00
abstract::Lenalidomide (LEN) acts directly on multiple myeloma (MM) cells by inducing cereblon-mediated degradation of interferon regulatory factor 4, Ikaros (IKZF)1 and IKZF3, transcription factors that are essential for MM cell survival. The mucin 1 (MUC1) C-terminal transmembrane subunit (MUC1-C) oncoprotein is aberrantly ex...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14801
更新日期:2017-09-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb04993.x
更新日期:1994-09-01 00:00:00
abstract::P-glycoprotein (Pgp) expression, which is associated with the multi-drug resistance (MDR) phenotype, has been reported to be a useful predictor of treatment outcome in acute leukaemia. We have examined the expression of Pgp on acute myeloid leukaemia (AML) cells in 54 newly diagnosed patients, using a novel streptavid...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb08305.x
更新日期:1994-07-01 00:00:00
abstract::An autoimmune mechanism in the pathogenesis of myelodysplastic syndrome (MDS) is suggested by response to immunosuppression, with CD8+ T-lymphocytes implicated in the haematopoietic suppression. We therefore sought evidence for human leucocyte antigen (HLA) restriction and variant frequency differences in selected pol...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03452.x
更新日期:2002-06-01 00:00:00
abstract::The chemotaxis of human malignant plasma cells is promoted by two extracellular matrix proteins (ECMs): fibronectin (FN) and laminin (LN). We examined the effect of the supernatant from a bone marrow stroma cell line, KM-101, on the chemotaxis of human malignant plasma cell lines to assess the chemotaxis-regulatory ro...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.d01-1691.x
更新日期:1996-06-01 00:00:00
abstract::Thirty-four patients with refractory multiple myeloma were treated with 4-d continuous infusions of vincristine and adriamycin in combination with 4-d pulsed high-dose dexamethasone (VAD). Of 31 evaluable patients, 16 entered a complete remission (50%) and three a partial remission (10%). No difference in response rat...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb06269.x
更新日期:1989-01-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
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更新日期:2018-05-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.7052322.x
更新日期:1996-09-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
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更新日期:1982-02-01 00:00:00
abstract::Myelodysplastic syndrome (MDS) is a common neoplasm of haematopoietic pluripotent stem cells. Although one third of MDS patients evolve to acute myeloid leukaemia (AML), little is understood about the mechanisms responsible for this progression. We have previously detected the frequent loss of heterozygosity (LOH) on ...
journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb03220.x
更新日期:1993-12-01 00:00:00
abstract::The success of genetically engineered T cells that express chimeric antigen receptors (CARTs) has been a momentous step forward in harnessing the potent cancer fighting abilities of the immune system. The efficacy seen in relapsed/refractory (r/r) acute lymphoblastic leukaemia (ALL), not only by inducing remission, bu...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
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更新日期:2017-04-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2017-05-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb02261.x
更新日期:1987-02-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2006.06223.x
更新日期:2006-09-01 00:00:00
abstract::The peripheral blood (PB) mononuclear cells in patients with multiple myeloma (MM) have been reported to include CD34-expressing cells that are clonally related to the myeloma cells. To determine whether there were elevated levels of CD34 mRNA or whether CD34+ cells in the PB include myeloma-related cells, we develope...
journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1982.tb03867.x
更新日期:1982-09-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12516
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb08177.x
更新日期:1992-05-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1975.tb00533.x
更新日期:1975-06-01 00:00:00
abstract::The 32 kD lipid-raft-associated membrane protein 'stomatin' is deficient from the erythrocyte membrane in the Na+-K+ leaky haemolytic anaemia, overhydrated hereditary stomatocytosis (OHSt). To date, no mutation in the gene coding for this protein has so far been found in OHSt. In this study, we have analysed the distr...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05742.x
更新日期:2005-10-01 00:00:00