Abstract:
:We studied the impact of driver mutations of JAK2, CALR, (calreticulin gene) or MPL on clinical course, leukemic transformation, and survival of patients with primary myelofibrosis (PMF). Of the 617 subjects studied, 399 (64.7%) carried JAK2 (V617F), 140 (22.7%) had a CALR exon 9 indel, 25 (4.0%) carried an MPL (W515) mutation, and 53 (8.6%) had nonmutated JAK2, CALR, and MPL (so-called triple-negative PMF). Patients with CALR mutation had a lower risk of developing anemia, thrombocytopenia, and marked leukocytosis compared with other subtypes. They also had a lower risk of thrombosis compared with patients carrying JAK2 (V617F). At the opposite, triple-negative patients had higher incidence of leukemic transformation compared with either CALR-mutant or JAK2-mutant patients. Median overall survival was 17.7 years in CALR-mutant, 9.2 years in JAK2-mutant, 9.1 years in MPL-mutant, and 3.2 years in triple-negative patients. In multivariate analysis corrected for age, CALR-mutant patients had better overall survival than either JAK2-mutant or triple-negative patients. The impact of genetic lesions on survival was independent of current prognostic scoring systems. These observations indicate that driver mutations define distinct disease entities within PMF. Accounting for them is not only relevant to clinical decision-making, but should also be considered in designing clinical trials.
journal_name
Bloodjournal_title
Bloodauthors
Rumi E,Pietra D,Pascutto C,Guglielmelli P,Martínez-Trillos A,Casetti I,Colomer D,Pieri L,Pratcorona M,Rotunno G,Sant'Antonio E,Bellini M,Cavalloni C,Mannarelli C,Milanesi C,Boveri E,Ferretti V,Astori C,Rosti V,Cervadoi
10.1182/blood-2014-05-578435subject
Has Abstractpub_date
2014-08-14 00:00:00pages
1062-9issue
7eissn
0006-4971issn
1528-0020pii
blood-2014-05-578435journal_volume
124pub_type
杂志文章相关文献
BLOOD文献大全abstract::An inactivating polymorphism at position 609 in the NAD(P)H:quinone oxidoreductase 1 gene (NQO1 C609T) is associated with an increased risk of adult leukemia. A small British study suggested that NQO1 C609T was associated with an increased risk of infant leukemias with MLL translocations, especially infant acute lymph...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2001-12-0264
更新日期:2002-12-15 00:00:00
abstract::Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myeloid neoplasm characterized by excessive proliferation of myelomonocytic cells. Somatic mutations in genes involved in GM-CSF signal transduction, such as NRAS, KRAS, PTPN11, NF1, and CBL, have been identified in more than 70% of children with JMML. In the...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-02-406090
更新日期:2012-08-16 00:00:00
abstract::Activation and subsequent differentiation of naive CD8+ T cells lead to the development of memory subsets with distinct homing and effector capacities. On nonlymphoid homing subsets, expression of "inflammatory" chemokine receptors (such as CXCR3, CCR5, CX3CR1, and CXCR1) is believed to promote migration into sites of...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-04-1366
更新日期:2005-12-01 00:00:00
abstract::Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes can alter gene expression, modulate the balance between Th1/Th2 responsiveness, and influence susceptibility for autoimmune disorders, infectious diseases, and cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20 ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-4160
更新日期:2006-05-15 00:00:00
abstract::The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-09-307264
更新日期:2011-07-21 00:00:00
abstract::Natural-killer (NK)-cell dysfunction and IFN-gamma deficiencies have been associated with increased incidence of both malignancy and infection. The immunologic basis of NK-cell defects in cancer-bearing hosts has not been extensively studied. Here, we demonstrate that multiple lineages of tumors, including thymoma, br...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-11-4535
更新日期:2006-07-01 00:00:00
abstract::Cells derived from human cord blood were recently used instead of bone marrow (BM) for transplantation. However, several questions concerning the potential of these cells to reconstitute the hematopoietic and immunologic system of the recipient and to induce a graft-versus-host disease (GVHD) remain unanswered. Here w...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::CD4+Foxp3+ regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft-versus-host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation. W...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-06-723783
更新日期:2016-12-15 00:00:00
abstract::The interleukin (IL)-22R1 chain of the heterodimeric IL-22 receptor is not expressed on normal leukocytes, but this receptor is expressed on T cells from anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large cell lymphoma (ALCL) patients. To investigate the consequences of aberrant expression of this receptor ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-285908
更新日期:2011-01-13 00:00:00
abstract::Hypodiploidy <40 chromosomes is an uncommon genetic feature of acute lymphoblastic leukemia (ALL) in both children and adults. It has long been clear by cytogenetic analyses, and recently confirmed by mutational profiling, that these cases may be further subdivided into 2 subtypes: near-haploid ALL with 24 to 30 chrom...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-10-743765
更新日期:2017-01-26 00:00:00
abstract::Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder with multiple and varied clinical manifestations. The biochemical defect in PNH resides in the incomplete enzymatic assembly of glycosylphosphatidylinositol (GPI) anchors used for surface protein attachment. In all patients tested thu...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::Hematopoietic stem cells purified from mouse bone marrow are quiescent with less than 2% of Lin- Hoechst(low)/Rhodamine(low) (Lin- Ho(low)/Rho(low)) and 10% to 15% of Lin-/Sca+ cells in S phase. These cells enter proliferative cycle and progress through G1 and into S phase in the presence of cytokines and 5% heat-inac...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-09-15 00:00:00
abstract::Leukocyte alpha4beta1 integrins regulate hematopoietic and lymphoid development, as well as the emigration of circulating cells to sites of inflammation. Because vascular cell adhesion molecule-1 (VCAM-1) binding to high-affinity alpha4beta1 is stable, these integrins can be detected and selectively precipitated from ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-12-4402
更新日期:2004-11-01 00:00:00
abstract::Serum response factor (SRF) is a ubiquitously expressed transcription factor and master regulator of the actin cytoskeleton. We have previously shown that SRF is essential for megakaryocyte maturation and platelet formation and function. Here we elucidate the role of SRF in neutrophils, the primary defense against inf...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-06-507582
更新日期:2014-05-08 00:00:00
abstract::Isocitrate dehydrogenase 1 mutation (IDH1-R132H) was recently identified in acute myeloid leukemia with normal cytogenetics. The mutant enzyme is thought to convert α-ketoglutarate to the pathogenic 2-hydroxyglutarate (2-HG) that affects DNA methylation via inhibition of ten-eleven translocation 2. However, the role o...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-09-601187
更新日期:2015-05-07 00:00:00
abstract::The effect of HbA and HbF on both the aggregation and deaggregation of deoxy HbS and deoxy HbCHarlem in concentrated phosphate buffers was studied by a turbidimetric method. Although pure deoxy HbA is fully soluble in 2.4 M potassium phosphate buffer, the same concentration of deoxy HbAS was insoluble in the same buff...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-03-01 00:00:00
abstract::Dickkopf-1 (DKK1), a soluble inhibitor of Wnt signaling secreted by multiple myeloma (MM) cells contributes to osteolytic bone disease by inhibiting the differentiation of osteoblasts. In this study, we tested the effect of anti-DKK1 therapy on bone metabolism and tumor growth in a SCID-rab system. SCID-rab mice were ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-09-047712
更新日期:2007-03-01 00:00:00
abstract::The process of dendritic cell (DC) maturation, critical for effective DC-based immunotherapy, also alters the proteasome such that peptides presented in the context of HLA class I are generated not by the constitutive proteasome, but by the immunoproteasome. Cytotoxic T lymphocytes (CTLs) induced by such DCs might not...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-04-083188
更新日期:2007-12-15 00:00:00
abstract::The binding of neutrophil beta2 integrin to intercellular adhesion molecule-1 (ICAM-1) expressed on the inflamed endothelium is critical for neutrophil arrest at sites of tissue inflammation. To quantify the strength and kinetics of this interaction, we measured the adhesion between chemotactically stimulated neutroph...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::A noninferiority study was performed comparing low-dose and standard-dose prophylactic platelet transfusions. A double-blind randomized controlled trial (RCT) was performed in 6 sites in 3 countries. Thrombocytopenic adults requiring prophylactic platelet transfusion were randomly allocated to standard-dose (300-600 x...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2008-09-178236
更新日期:2009-02-12 00:00:00
abstract::Interleukin-12 (IL-12) inhibits angiogenesis in vivo by inducing interferon-gamma (IFN-gamma) and other downstream mediators. Here, we report that neutralization of natural killer (NK) cell function with antibodies to either asialo GM1 or NK 1.1 reversed IL-12 inhibition of basic fibroblast growth factor (bFGF)-induce...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-03-01 00:00:00
abstract::In patients with common variable immunodeficiency (CVI), we have previously defined a subgroup of patients (CVIHyper) characterized by decreased numbers of CD4+ lymphocytes in peripheral blood, splenomegaly, and persistent immune activation in vivo, particularly of monocytes/macrophages. To further characterize this h...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-01-15 00:00:00
abstract::We used our recently reported stable, transformed human renal carcinoma cell line as a model system to study the role of 3',5'-adenosine monophosphate (cAMP) in erythropoietin secretion. The erythropoietin produced by these cells is both biologically active and immunologically cross-reactive with purified native human...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::Transformation to aggressive lymphoma is a critical event in the clinical course of follicular lymphoma (FL) patients. Yet, it is a challenge to reliably predict transformation at the time of diagnosis. Understanding the risk of transformation would be useful for guiding and monitoring patients, as well as for evaluat...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2017-03-691345
更新日期:2017-07-20 00:00:00
abstract::T-cell dysfunction after human hematopoietic stem-cell transplantation (HSCT) is generally attributed to intrinsic T-cell defects. Here we show that the characteristic impaired proliferative responses to polyclonal stimulation of post-HSCT peripheral blood mononuclear cells (PB-MCs) were markedly (4-fold) improved by ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-05-1726
更新日期:2005-05-15 00:00:00
abstract::We took advantage of the proliferative and permissive environment of the developing preimmune fetus to develop a noninjury large animal model in sheep, in which the transplantation of defined populations of human hematopoietic stem cells resulted in the establishment of human hematopoiesis and led to the formation of ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-01-0259
更新日期:2004-10-15 00:00:00
abstract::Exposure to ambient particulate matter (PM) air pollution has been reported to trigger inflammation and thrombosis. However, molecular mechanisms underlying the modulation of coagulation pathways in PM-induced thrombosis remain largely unknown. We report here that Sirt1, a member of class III histone deacetylase, cont...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-04-350413
更新日期:2012-03-08 00:00:00
abstract::We prepared a heterohybrid cell line that secretes a human IgM monoclonal autoantibody that recognizes an antigen found on thrombin-activated or stored platelets. The surface expression of the epitope recognized by this autoantibody, 5E5, increases with time as platelets age in vitro, suggesting that it may represent ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is initiated and driven by the oncogenic fusion protein BCR-ABL, a constitutively active tyrosine kinase. Despite major advances in the treatment of this highly aggressive disease with potent inhibitors of the BCR-ABL kinase such as dasatinib, pat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-09-601062
更新日期:2015-02-26 00:00:00
abstract::Interleukin 2 (IL-2) rescued human natural killer (NK) KHYG-1 cells from apoptosis along with a reduction of ceramide. Conversely, an increase of ceramide inhibited IL-2-rescued survival. IL-2 deprivation-induced activation of acid sphingomyelinase (SMase) and inhibition of glucosylceramide synthase (GCS) and sphingom...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-03-0900
更新日期:2004-11-15 00:00:00