12,262 results match your criteria Myeloproliferative Disease


Left ventricular ball-like thrombus after acute myocardial infarction with essential thrombocythemia.

J Cardiol Cases 2014 Jul 10;10(1):1-3. Epub 2014 May 10.

Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.

Left ventricular (LV) thrombus after acute myocardial infarction (AMI) is a frequent complication that is associated with a risk of systemic embolism. Essential thrombocythemia (ET) has opposing tendencies towards hemorrhage and thrombogenesis and it can cause AMI via thrombogenesis. Ball-like LV thrombus is associated with a high risk of systemic embolism. Read More

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International external quality assurance of JAK2 V617F quantification.

Ann Hematol 2018 Dec 8. Epub 2018 Dec 8.

Department of Hematology, Zealand University Hospital, Roskilde, Denmark.

External quality assurance (EQA) programs are vital to ensure high quality and standardized results in molecular diagnostics. It is important that EQA for quantitative analysis takes into account the variation in methodology. Results cannot be expected to be more accurate than limits of the technology used, and it is essential to recognize factors causing substantial outlier results. Read More

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December 2018
2.634 Impact Factor

[Regulation of hematopoietic stem cell homeostasis by Spred1].

Rinsho Ketsueki 2018 ;59(11):2441-2448

Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University.

Various types of stresses account for the dysregulation of the self-renewal activity of stem cells, resulting in the functional failure of tissues or tumorigenesis promotion. Although diets also affect our health, the effect of harmful dietary stresses on the tissue or stem cell homeostasis remains unclear. Recent research has revealed that Spred1, which negatively regulates RAS-MAPK signaling, protects hematopoietic stem cell (HSC) homeostasis against high-fat diet (HFD) -induced systemic stress. Read More

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January 2018

AACR White Paper: Shaping the Future of Cancer Prevention - A Roadmap for Advancing Science and Public Health.

Cancer Prev Res (Phila) 2018 Dec;11(12):735-778

Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX.

The recent pace, extent, and impact of paradigm-changing cancer prevention science has been remarkable. The American Association for Cancer Research (AACR) convened a 3-day summit, aligned with five research priorities: (i) Precancer Atlas (PCA). (ii) Cancer interception. Read More

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December 2018

Heterogeneity in myeloproliferative neoplasms: Causes and consequences.

Adv Biol Regul 2018 Nov 22. Epub 2018 Nov 22.

MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, United Kingdom; NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK. Electronic address:

Myeloproliferative neoplasms (MPNs) are haematopoietic stem cell-derived clonal disorders characterised by proliferation of some or all myeloid lineages, depending on the subtype. MPNs are classically categorized into three disease subgroups; essential thrombocythaemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF). The majority (>85%) of patients carry a disease-initiating or driver mutation, the most prevalent occurring in the janus kinase 2 gene (JAK2 V617F), followed by calreticulin (CALR) and myeloproliferative leukaemia virus (MPL) genes. Read More

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November 2018

Trisomy silencing by XIST normalizes Down syndrome cell pathogenesis demonstrated for hematopoietic defects in vitro.

Nat Commun 2018 12 5;9(1):5180. Epub 2018 Dec 5.

Department of Neurology and Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA.

We previously demonstrated that an integrated XIST transgene can broadly repress one chromosome 21 in Down syndrome (DS) pluripotent cells. Here we address whether trisomy-silencing can normalize cell function and development sufficiently to correct cell pathogenesis, tested in an in vitro model of human fetal hematopoiesis, for which DS cellular phenotypes are best known. XIST induction in four transgenic clones reproducibly corrected over-production of megakaryocytes and erythrocytes, key to DS myeloproliferative disorder and leukemia. Read More

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December 2018

Exploring the reason for increased activity of SHP2 caused by D61Y mutation through molecular dynamics.

Comput Biol Chem 2018 Oct 29;78:133-143. Epub 2018 Oct 29.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China. Electronic address:

Juvenile myelomonocytic leukaemia, an aggressive myeloproliferative neoplasm, is characterized by thrombocytopenia, splenomegaly, fever and excess myelomonocytic cells. Approximately 35% of patients with JMML occur D61Y mutation in PTPN11, and it increases the activity of the protein. However, the effect of the D61Y mutation on SHP2 conformations in molecular basis is poorly understood. Read More

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October 2018
1 Read

Spurious Laboratory Values in Patients With Leukocytosis.

Crit Care Nurs Q 2019 Jan/Mar;42(1):44-46

Emergency Department, Bellevue Hospital Center, NYU School of Medicine, New York (Mr Malek); and Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, and NYU Rory Meyers College of Nursing, New York (Dr Chen).

Physiological derangements such as hypoxemia and hyperkalemia are medical emergencies that warrant prompt interventions to prevent further patient clinical deterioration. However, in patients with myeloproliferative diseases or malignancies that result in extreme leukocytosis, hypoxemia and hyperkalemia demonstrated in laboratory results could be deceiving due to in vitro reactions and may not reflect actual patient condition. Clinicians have to be familiar with these phenomena so as to not cause harm by treating these spurious laboratory values. Read More

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December 2018
1 Read

JMML genomics and decisions.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):307-312

Department of Pediatrics and Adolescent Medicine, University Children's Hospital, University of Freiburg, Freiburg, Germany.

Juvenile myelomonocytic leukemia (JMML) is a unique clonal hematopoietic disorder of early childhood characterized by hyperactivation of the RAS signal transduction pathway. Approximately 90% of patients harbor molecular alteration in 1 of 5 genes (), which define genetically and clinically distinct JMML subtypes. Three subtypes, , and -mutated JMML, are characterized by heterozygous somatic gain-of-function mutations in non syndromic children, while two subtypes, JMML in neurofibromatosis type 1 and in JMML in children with CBL syndrome, are characterized by germ line RAS disease and acquired biallelic inactivation of the respective tumor suppressor genes in hematopoietic cells. Read More

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November 2018
1 Read

Managing myelofibrosis (MF) that "blasts" through: advancements in the treatment of relapsed/refractory and blast-phase MF.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):118-126

Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX.

Myelofibrosis (MF) is the most aggressive form of Philadelphia chromosome-negative myeloproliferative neoplasm, and it is complicated by severe symptom burden, thrombotic events, infections, cytopenias, and transformation to acute myeloid leukemia (AML). Ruxolitinib, the first-line therapy for symptomatic or intermediate- and high-prognostic risk MF, has improved overall survival for this population. However, approximately one-half of MF patients will discontinue ruxolitinib by the first few years of therapy due to a spectrum of resistance, intolerance, relapse, or progression to blast phase disease. Read More

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November 2018
1 Read

JAK2 (and other genes) be nimble with MPN diagnosis, prognosis, and therapy.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):110-117

Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and.

Now that the spectrum of somatic mutations that initiate, propagate, and drive the progression of myeloproliferative neoplasms (MPNs) has largely been defined, recent efforts have focused on integrating this information into clinical decision making. In this regard, the greatest progress has been made in myelofibrosis, in which high-molecular-risk mutations have been identified and incorporated into prognostic models to help guide treatment decisions. In this chapter, we focus on advances in 4 main areas: (1) What are the MPN phenotypic driver mutations? (2) What constitutes high molecular risk in MPN (focusing on )? (3) How do we risk-stratify patients with MPN? And (4) What is the significance of molecular genetics for MPN treatment? Although substantial progress has been made, we still have an incomplete understanding of the molecular basis for phenotypic diversity in MPN, and few rationally designed therapeutic approaches to target high-risk mutations are available. Read More

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November 2018
1 Read

Somatic Mutations in Philadelphia Chromosome-Negative Myeloproliferative Neoplasms.

Semin Hematol 2018 Oct 17;55(4):215-222. Epub 2018 Apr 17.

Serviço de Hematologia e Transplantação de Medula, Hospital de Santa Maria, Lisboa, Portugal.

Myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPN are characterized by clonal proliferation of myeloid progenitors leading to erythrocytosis, thrombocytosis, or leukocytosis, and risk of hemorrhagic and thrombotic events, as well as myelofibrosis and blast transformation. The discovery of somatic mutations in MPN, namely JAK2 V617F, JAK2 exon 12, MPL, and CALR mutations, has permitted a more specific approach to diagnosis and treatment. Read More

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October 2018
2 Reads

The germline JAK2 GGCC (46/1) haplotype and survival among 414 molecularly-annotated patients with primary myelofibrosis.

Am J Hematol 2018 Dec 5. Epub 2018 Dec 5.

Division of Hematology, Mayo Clinic, Rochester, Minnesota.

JAK2 mutations in myeloproliferative neoplasms (MPNs) are associated with the germline GGCC (46/1) haplotype. In 2010, we reported an association between shortened survival in primary myelofibrosis (PMF) and nullizygosity for the JAK2 46/1 haplotype. In the current study, we have increased the number of informative cases from 130 to 414 (median age 63 years; 63% males), in order to revisit with the phenotypic and prognostic relevance of the JAK2 46/1 haplotype in PMF. Read More

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December 2018
1 Read

Aberrant histone modifications induced by mutant ASXL1 in myeloid neoplasms.

Int J Hematol 2018 Dec 5. Epub 2018 Dec 5.

Division of Cellular Therapy, Advanced Clinical Research Center, Division of Stem Cell Signaling, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 1088639, Japan.

An epigenetic modulator Additional sex combs-like 1 (ASXL1) is recurrently mutated in myeloid neoplasms such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs). ASXL1 mutations are also frequently detected in clonal hematopoiesis with indeterminate potential (CHIP), which is the clonal expansion of premalignant hematopoietic cells without any evidence of hematological malignancies. Thus, understanding the roles of ASXL1 in hematopoiesis and myeloid neoplasms is a clinically crucial issue. Read More

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December 2018
1 Read

JAK2-tree: a simple CBC-based decision rule to guide appropriate JAK2 V617F mutation testing.

J Clin Pathol 2018 Dec 4. Epub 2018 Dec 4.

Division of Haematology, Calgary Lab Services & Department of Pathology & Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.

Aims: The JAK2 V617F mutation is highly recurrent in many of the myeloproliferative neoplasms, a molecular variant that can be easily detected using sensitive and minimally invasive techniques. Given the ease of JAK2 V617F testing, this test may be improperly requested for the purposes of patient 'screening' and to optimise laboratory resource utilisation, it behooves clinicians and laboratorians to perform JAK2 V617F testing only when most appropriate.

Methods: To assist with the screening of patients being considered for JAK2 V617F testing, we developed a clinical decision rule, "JAK2-tree", which can be easily applied to basic CBC parameters (haemoglobin, platelet and white blood cell counts). Read More

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December 2018
1 Read

Philadelphia chromosome positive AML arising from JAK2-positive myelofibrosis.

Biomark Res 2018 21;6:33. Epub 2018 Nov 21.

6Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: A feature of myeloproliferative neoplasia is transforming to more aggressive and malignant myeloid neoplasia, including acute myeloid leukemia. Different pathogenesis mechanisms participate in transformation, including transformation of existing potential preleukemic clones, since -mutant myeloproliferative neoplasms often transform to wild-type acute myeloid leukemia.

Case Presentation: Here, we present an 80 year old man with a -V617F mutant primary myelofibrosis. Read More

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November 2018
8 Reads

Different effect of hydroxyurea and phlebotomy on prevention of arterial and venous thrombosis in Polycythemia Vera.

Blood Cancer J 2018 Nov 26;8(12):124. Epub 2018 Nov 26.

Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative neoplasms (CRIMM), AOU Careggi, University of Florence, Florence, Italy.

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November 2018
2 Reads

Knockout of both miR-15/16 loci induces acute myeloid leukemia.

Proc Natl Acad Sci U S A 2018 Nov 26. Epub 2018 Nov 26.

Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210;

MicroRNAs (miRNAs) have been extensively reported to be associated with hematological malignancies. The loss of miR-15a/16-1 at chromosome 13q14 is a hallmark of most of human chronic lymphocytic leukemia (CLL). Deletion of murine miR-15a/16-1 and miR-15b/16-2 has been demonstrated to promote B cell malignancies. Read More

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November 2018
2 Reads

[Advances in the treatment of juvenile myelomonocytic leukemia].

Zhongguo Dang Dai Er Ke Za Zhi 2018 Nov;20(11):958-963

Department of Pediatrics, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin 300020, China.

Juvenile myelomonocytic leukemia (JMML) is a rare chronic myeloid leukemia in children and has the features of both myelodysplastic syndrome and myeloproliferative neoplasm. It is highly malignant and has a poor treatment outcome. Children with JMML have a poor response to conventional chemotherapy. Read More

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November 2018
2 Reads

Colony-stimulating Factor 3 Receptor Mutated Chronic Neutrophilic Leukemia: A Rare Case Report.

Cureus 2018 Sep 18;10(9):e3326. Epub 2018 Sep 18.

Hematology and Oncology, Cleveland Clinic - Fairview Hospital, Cleveland, USA.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm, which is characterized by sustained peripheral leukocytosis with neutrophilia, hepatosplenomegaly, and hypercellularity of the bone marrow, with less than 5% myeloblasts along with normal neutrophil maturation and no dysplasia. In 2016, World Health Organization (WHO) included activating mutations in the gene for colony-stimulating factor 3 receptor (CSF3R) as one of the diagnostic criteria with CSF3RT618I being the most common mutation. We report a rare case of CNL (JAK2V617F negative, BCR-ABL1 negative, CSF3RT618I positive) in an elderly female who had an aggressive clinical course of the disease. Read More

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September 2018
2 Reads

Singular Case of Osteolytic Lesions Revealing Transformation of Myeloproliferative Syndrome to Acute Leukemia.

Joint Bone Spine 2018 Nov 21. Epub 2018 Nov 21.

Service de rhumatologie, CHU d'Angers, 4 rue Larrey, 49933 Angers cedex 9, France; Groupe d'Eudes Remodelage Osseux et bioMatériaux LHEA UPRES EA 4658, CHU d'Angers, 4 rue Larrey, 49933 Angers cedex 9, France. Electronic address:

Hematological malignancies can cause bone lesions, of which the most common are the punched-out foci of osteolysis seen in multiple myeloma. However, osteosclerotic lesions are more common. We report the unusual case of a patient with myeloproliferative syndrome in whom the development of osteolytic lesions revealed transformation to acute leukemia. Read More

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November 2018
7 Reads

JAK2V617F but not CALR mutations confer increased molecular responses to interferon-α via JAK1/STAT1 activation.

Leukemia 2018 Nov 23. Epub 2018 Nov 23.

Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.

Pegylated interferon-α (peg-IFNa) treatment induces molecular responses (MR) in patients with myeloproliferative neoplasms (MPNs), including partial MR (PMR) in 30-40% of patients. Here, we compared the efficacy of IFNa treatment in JAK2V617F- vs. calreticulin (CALR)-mutated cells and investigated the mechanisms of differential response. Read More

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November 2018
4 Reads

A case of positive myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Turk J Haematol 2018 Nov 23. Epub 2018 Nov 23.

Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.

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November 2018
1 Read

Leukemia development initiated by deletion of RBP-J: mouse strain, deletion efficiency, and cell of origin.

Dis Model Mech 2018 Nov 22. Epub 2018 Nov 22.

Department of Pediatrics, University of Virginia School of Medicine, MR4 Building, 409 Lane Road, Charlottesville, VA 22908, USA.

Conditional deletion of , the major transcriptional effector of Notch signaling, specifically within renin-expressing cells leads to the development of B cell leukemia. However, the influence of contributing factors such as mouse strain, cell of origin, and cre recombinase copy number are unknown. In this study, we compared deletion efficiency using 1 versus 2 copies of cre recombinase. Read More

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November 2018
5 Reads

Unique Case of Myeloproliferative Neoplasm with Two Rare Clonal Abnormalities: Rare JAK2 Exon 12 Mutation and Rare e14a3 (b3a3) BCR/ABL Fusion Transcript.

Acta Haematol 2018 Nov 21;141(1):23-27. Epub 2018 Nov 21.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas,

Myeloproliferative neoplasms (MPNs) are clonal disorders divided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) or Ph chromosome-negative MPNs. Co-occurrence of these disease entities is very rare and typically involves presence of common p190 or p210 BCR/ABL fusion transcript (responsible for CML) along with JAK2V617F mutation (most common driver mutation in Ph-negative MPNs). Because of the rarity of such cases, it is not clear if the outcomes are any different in these patients. Read More

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November 2018
2 Reads

Comorbidities in polymyalgia rheumatica: a systematic review.

Arthritis Res Ther 2018 Nov 20;20(1):258. Epub 2018 Nov 20.

Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, Keele, ST5 5BG, UK.

Background And Aim: Comorbidities are known to exist in many rheumatological conditions. Polymyalgia rheumatica (PMR) is a common inflammatory rheumatological condition affecting older people which, prior to effective treatment, causes severe disability. Our understanding of associated comorbidities in PMR is based only on case reports or series and small cohort studies. Read More

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November 2018
3 Reads

Extramedullary hematopoiesis in the absence of myeloproliferative neoplasm: Mayo Clinic case series of 309 patients.

Blood Cancer J 2018 Nov 19;8(12):119. Epub 2018 Nov 19.

Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.

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November 2018
1 Read

Analysis of clinical characteristics of bone marrow proliferative tumor progression to acute myeloid leukemia.

Cancer Biomark 2018 Nov 4. Epub 2018 Nov 4.

Objective: This study aims to analyze Chinese patients who developed acute leukemia after being diagnosed and treated for Philadelphia chromosome (Ph)-negative chronic myeloproliferative neoplasms (MPNs), and compare the findings of this series with similar studies from literature.

Methods: Nine patients who progressed to leukemia after being diagnosed with MPN were included into the present study. Clinical data including age, treatment modalities and duration of use in the myeloproliferative phase, latency to leukemic transformation (LT), characteristics of leukemia, chemotherapy administration, and survival after LT were examined. Read More

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November 2018
1 Read

Frequency and etiology of pulmonary hypertension in patients with myeloproliferative neoplasms.

Eur J Haematol 2018 Nov 19. Epub 2018 Nov 19.

Department of Haematology, Odense University Hospital, Denmark.

Objective: Pulmonary hypertension (PH) has been reported to be associated with myeloproliferative neoplasms (MPN), affecting 5-48% of MPN patients. With the aims to describe the prevalence of PH in Ph-MPN patients and explore the cause in identified subjects, we performed a prospective cohort study of Ph-MPN patients.

Method: Transthoracic echocardiography (TTE) was performed on all patients. Read More

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November 2018
5 Reads

EXPAND, a dose-finding study of ruxolitinib in patients with myelofibrosis and low platelet counts: 48-week follow-up analysis.

Haematologica 2018 Nov 15. Epub 2018 Nov 15.

Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna.

EXPAND (phase 1b, dose-finding study) evaluated the starting dose of ruxolitinib in patients with myelofibrosis with baseline platelet counts of 50-99x10/L. The study consisted of dose-escalation and safety-expansion phases. Based on the baseline platelet counts, patients were assigned to stratum 1 (75-99x10/L) or stratum 2 (50-74x10/L), with the primary objective of determining the maximum safe starting dose; key secondary objectives included safety and efficacy. Read More

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November 2018
8 Reads

Serum cytokine levels differ according to major cardiovascular risk factors in patients with lower limb atherosclerosis.

Cytokine 2018 Nov 13. Epub 2018 Nov 13.

Department of Vascular Surgery, Turku University Hospital and Turku University, Turku, Finland.

Different cardiovascular risk factors present a heterogenic manifestation of lower limb atherosclerosis. The molecular mechanisms behind this phenomenon remain unknown. We aimed to clarify this phenomenon by studying the association of major cardiovascular risk factors with the profile of serum cytokines in 226 consecutive patients with lower limb atherosclerosis treated at a department of Vascular Surgery during a one-year enrollment period. Read More

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November 2018
5 Reads

MLL-PTD in a 13-year-old patient with blast phase myeloproliferative neoplasm: A case report.

Medicine (Baltimore) 2018 Nov;97(46):e13220

Department of Hematology, Union Hospital, Fujian Medical University, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fuzhou, China.

Rationale: The risk of leukemic transformation in myeloproliferative neoplasm (MPN) has been increasing with time. Partial Tandem Duplications of the MLL gene (MLL-PTD) has been reported in de novo acute myeloid leukemia (AML), but not in MPN blast phase. The post-MPN AML developed adverse clinical outcomes, which showed no noticeable improvement over the past 15 years. Read More

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November 2018
6 Reads

Targeting the CALR interactome in myeloproliferative neoplasms.

JCI Insight 2018 Nov 15;3(22). Epub 2018 Nov 15.

Human Oncology and Pathogenesis Program.

Mutations in the ER chaperone calreticulin (CALR) are common in myeloproliferative neoplasm (MPN) patients, activate the thrombopoietin receptor (MPL), and mediate constitutive JAK/STAT signaling. The mechanisms by which CALR mutations cause myeloid transformation are incompletely defined. We used mass spectrometry proteomics to identify CALR-mutant interacting proteins. Read More

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November 2018
8 Reads

Mutations and prognosis in myeloproliferative neoplasms.

Leuk Lymphoma 2018 Nov 14:1-2. Epub 2018 Nov 14.

a Division of Hematology, Department of Internal Medicine , Mayo Clinic , Rochester , MN , USA.

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November 2018

Recent Studies on Ponatinib in Cancers Other Than Chronic Myeloid Leukemia.

Cancers (Basel) 2018 Nov 9;10(11). Epub 2018 Nov 9.

Department of Pharmacy, University of Genova, Viale Benedetto XV 3, 16132 Genova, Italy.

Ponatinib is a third line drug for the treatment of chronic myeloid leukemia patients, especially those that develop the gatekeeper mutation T315I, which is resistant to the first and the second line drugs imatinib, nilotinib, dasatinib and bosutinib. The compound was first identified as a pan Bcr-Abl and Src kinase inhibitor. Further studies have indicated that it is a multitargeted inhibitor that is active on FGFRs, RET, AKT, ERK1/2, KIT, MEKK2 and other kinases. Read More

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November 2018
2 Reads

JARID2 Functions as a Tumor Suppressor in Myeloid Neoplasms by Repressing Self-Renewal in Hematopoietic Progenitor Cells.

Cancer Cell 2018 Nov;34(5):741-756.e8

Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Developmental, Regenerative and Stem Cell Biology Program, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

How specific genetic lesions contribute to transformation of non-malignant myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDSs) to secondary acute myeloid leukemia (sAML) are poorly understood. JARID2 is lost by chromosomal deletions in a proportion of MPN/MDS cases that progress to sAML. In this study, genetic mouse models and patient-derived xenografts demonstrated that JARID2 acts as a tumor suppressor in chronic myeloid disorders. Read More

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November 2018
14 Reads
23.523 Impact Factor

The Myc/Max/Mxd Network Is a Target of Mutated Flt3 Signaling in Hematopoietic Stem Cells in Flt3-ITD-Induced Myeloproliferative Disease.

Stem Cells Int 2018 21;2018:3286949. Epub 2018 Oct 21.

Hematopoietic Stem Cell Laboratory, Lund Stem Cell Center, Lund University, Klinikgatan 26, 221 84 Lund, Sweden.

Acute myeloid leukemia (AML) has poor prognosis due to various mutations, e.g., in the FLT3 gene. Read More

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October 2018
8 Reads

Challenges in the introduction of next-generation sequencing (NGS) for diagnostics of myeloid malignancies into clinical routine use.

Blood Cancer J 2018 Nov 12;8(11):113. Epub 2018 Nov 12.

Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Given the vast phenotypic and genetic heterogeneity of acute and chronic myeloid malignancies, hematologists have eagerly awaited the introduction of next-generation sequencing (NGS) into the routine diagnostic armamentarium to enable a more differentiated disease classification, risk stratification, and improved therapeutic decisions. At present, an increasing number of hematologic laboratories are in the process of integrating NGS procedures into the diagnostic algorithms of patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs). Inevitably accompanying such developments, physicians and molecular biologists are facing unexpected challenges regarding the interpretation and implementation of molecular genetic results derived from NGS in myeloid malignancies. Read More

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November 2018
4 Reads

Hydroxyurea prevents arterial and late venous thrombotic recurrences in patients with myeloproliferative neoplasms but fails in the splanchnic venous district. Pooled analysis of 1500 cases.

Blood Cancer J 2018 Nov 12;8(11):112. Epub 2018 Nov 12.

FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy.

We collected 1500 patients with myeloproliferative neoplasms (MPN) and arterial or venous thrombosis (935/565), pooling three independent cohorts previously reported. Long-term treatment with antiplatelet drugs or vitamin K-antagonists (VKA) was given to 1391 (92.7%) patients; 975 (65%) patients received hydroxyurea (HU). Read More

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November 2018

MiR-10a and HOXB4 are overexpressed in atypical myeloproliferative neoplasms.

BMC Cancer 2018 Nov 12;18(1):1098. Epub 2018 Nov 12.

INSERM U1035, Université de Bordeaux, Bordeaux, France.

Background: Atypical Myeloproliferative Neoplasms (aMPN) share characteristics of MPN and Myelodysplastic Syndromes. Although abnormalities in cytokine signaling are common in MPN, the pathophysiology of atypical MPN still remains elusive. Since deregulation of microRNAs is involved in the biology of various cancers, we studied the miRNome of aMPN patients. Read More

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November 2018
7 Reads

Megakaryocyte Contribution to Bone Marrow Fibrosis: many Arrows in the Quiver.

Mediterr J Hematol Infect Dis 2018 1;10(1):e2018068. Epub 2018 Nov 1.

Department of Molecular Medicine, University of Pavia, Pavia, Italy.

In Primary Myelofibrosis (PMF), megakaryocyte dysplasia/hyperplasia determines the release of inflammatory cytokines that, in turn, stimulate stromal cells and induce bone marrow fibrosis. The pathogenic mechanism and the cells responsible for progression to bone marrow fibrosis in PMF are not completely understood. This review article aims to provide an overview of the crucial role of megakaryocytes in myelofibrosis by discussing the role and the altered secretion of megakaryocyte-derived soluble factors, enzymes and extracellular matrices that are known to induce bone marrow fibrosis. Read More

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November 2018
2 Reads

The JAK2V617F Point Mutation Increases the Osteoclast Forming Ability of Monocytes in Patients with Chronic Myeloproliferative Neoplasms and Makes their Osteoclasts more Susceptible to JAK2 Inhibition.

Mediterr J Hematol Infect Dis 2018 1;10(1):e2018058. Epub 2018 Nov 1.

Department of Hematology, Democritus University of Thrace, Alexandroupolis, Greece.

is a gain of function point mutation that occurs in Myeloproliferative Neoplasm (MPN) patients and deranges their hemopoiesis at cellular level. We speculate that hyperfunctioning JAK2 can modify osteoclast (OCL) homeostasis in MPN patients. We studied 18 newly diagnosed MPN patients and four age-matched normal donors (ND). Read More

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November 2018
1 Read

Mayo alliance prognostic system for mastocytosis: clinical and hybrid clinical-molecular models.

Blood Adv 2018 Nov;2(21):2964-2972

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.

Systemic mastocytosis (SM) is a clinically heterogeneous disease with prognosis chiefly assigned based on World Health Organization (WHO) morphologic subclassification. We assessed the feasibility of developing contemporary risk models for SM based on clinical and integrated clinical-genetics information. Diagnosis of SM was per WHO criteria, and karyotype and next-generation sequencing data were available in a subset of the total 580 patients (median age, 55 years; range, 18-88 years) seen at the Mayo Clinic between 1968 and 2015. Read More

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November 2018
7 Reads

Recommendations for the use of pegylated interferon-α in the treatment of classical myeloproliferative neoplasms.

Intern Med J 2018 Nov 8. Epub 2018 Nov 8.

Department of Haematology, Royal Adelaide Hospital and Flinders Medical Centre, and Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA.

The classical myeloproliferative neoplasms (MPN) are uncommon clonal haematopoietic malignancies characterised by excessive production of mature blood cells. Clinically they are associated with thrombosis, haemorrhage, varying degrees of constitutional disturbance, and a risk of progression to myelofibrosis or acute myeloid leukaemia. Many of the disease manifestations may be ameliorated by treatment with interferon-α (IFN) but its use in Australian MPN patients has been limited due to the inconvenience of frequent injections and side effects. Read More

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November 2018
6 Reads

Preservation of Quiescent Chronic Myelogenous Leukemia Stem Cells by the Bone Marrow Microenvironment.

Adv Exp Med Biol 2018 ;1100:97-110

Division of Hematology & Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

The majority of leukemia patients achieving remission ultimately relapse. Persistence of leukemia stem cells (LSC) capable of regenerating leukemia is a major cause of relapse. There is a pressing need to better understand mechanisms of LSC regulation and their resistance to therapy in order to improve outcomes for leukemia. Read More

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January 2018
5 Reads

The sympathomimetic agonist mirabegron did not lower JAK2-V617F allele burden, but restored nestin-positive cells and reduced reticulin fibrosis in patients with myeloproliferative neoplasms: results of phase 2 study SAKK 33/14.

Haematologica 2018 Nov 8. Epub 2018 Nov 8.

Dept of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel

The β-3 sympathomimetic agonist BRL37344 restored nestin-positive cells within the stem cell niche, and thereby normalized blood counts and improved myelofibrosis in a mouse model of JAK2-V617F positive myeloproliferative neoplasms. We therefore tested the effectiveness of mirabegron, a β-3 sympathomimetic agonist, in a phase II trial including 39 JAK2-V617F positive MPN with a mutant allele burden >20%. Treatment consisted of mirabegron 50 mg daily for 24 weeks. Read More

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November 2018
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New Classification for Myeloproliferative Neoplasms.

Authors:

Cancer Discov 2018 Dec 8;8(12):OF1. Epub 2018 Nov 8.

Myeloproliferative neoplasms have traditionally been split into three categories, but a new study that analyzed mutations in more than 2,000 patients suggests dividing the illness into eight subtypes. Using statistical models that incorporated clinical and genomic data, researchers accurately predicted overall survival and the likelihood of disease progression. Read More

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December 2018
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Modeling human RNA spliceosome mutations in the mouse: not all mice were created equal.

Exp Hematol 2018 Nov 6. Epub 2018 Nov 6.

St. Vincent's Institute, Fitzroy, Victoria 3065, Australia; Department of Medicine, St. Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia; Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria 3000, Australia. Electronic address:

Myelodysplastic syndromes (MDS) and related myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are clonal stem cell disorders, primarily affecting patients over 65 years of age. Mapping of the MDS and MDS/MPN genome identified recurrent heterozygous mutations in the RNA splicing machinery, with the SF3B1, SRSF2, and U2AF1 genes being frequently mutated. To better understand how spliceosomal mutations contribute to MDS pathogenesis in vivo, numerous groups have sought to establish conditional murine models of SF3B1, SRSF2, and U2AF1 mutations. Read More

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November 2018
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Sequential B-lymphoid and myeloid blastic transformation of Philadelphia chromosome-negative myeloproliferative neoplasm.

Br J Haematol 2018 Nov 8. Epub 2018 Nov 8.

Department of Immunology & Pathology, Baylor College of Medicine, Houston, TX, USA.

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November 2018
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