559 results match your criteria transient myeloproliferative

JAK 2 positive myeloproliferative neoplasm presenting as stroke, recurrent TIA and isolated third nerve palsy.

BMJ Case Rep 2021 Jun 10;14(6). Epub 2021 Jun 10.

Stroke Medicine, New Cross Hospital, Wolverhampton, UK.

A man in his early 40s with no significant vascular risk factors was managed within a period of 6 months for recurrent vascular events: ischaemic stroke, transient ischaemic attack and isolated third nerve palsy. He was extensively investigated throughout the course of illness. The only potential aetiological factor identified was a positive janus kinase 2 (JAK 2) mutation after screening on account of mildly elevated platelet count noted during his most recent admission. Read More

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The value of bone marrow, liver, and spleen imaging in diagnosis, prognostication, and follow-up monitoring of myeloproliferative neoplasms: a systematic review.

Cancer Imaging 2021 Apr 20;21(1):36. Epub 2021 Apr 20.

Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.

Background: Diagnostic and treatment response criteria for the JAK2/CALR/MPL mutation-related myeloproliferative neoplasms (MPNs) are largely based on bone marrow (BM) biopsy results. However, these biopsies have several limitations, such as the risk of sampling error. Also, the prognostic impact of BM abnormalities is largely unclear. Read More

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Juvenile myelomonocytic leukemia-A comprehensive review and recent advances in management.

Am J Blood Res 2021 15;11(1):1-21. Epub 2021 Feb 15.

Division of Pediatric Oncology, Department of Pediatrics, All India Institute of Medical Sciences New Delhi 110029, India.

Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myelodysplastic/myeloproliferative neoplasm overlap disease. JMML is associated with mutations in the RAS pathway genes resulting in the myeloid progenitors being sensitive to granulocyte monocyte colony-stimulating factor (GM-CSF). Karyotype abnormalities and additional epigenetic alterations can also be found in JMML. Read More

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February 2021

Molecular Mechanisms of the Genetic Predisposition to Acute Megakaryoblastic Leukemia in Infants With Down Syndrome.

Front Oncol 2021 11;11:636633. Epub 2021 Mar 11.

Pediatric Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany.

Individuals with Down syndrome are genetically predisposed to developing acute megakaryoblastic leukemia. This myeloid leukemia associated with Down syndrome (ML-DS) demonstrates a model of step-wise leukemogenesis with perturbed hematopoiesis already presenting , facilitating the acquisition of additional driver mutations such as truncating variants, which are pathognomonic to the disease. Consequently, the affected individuals suffer from a transient abnormal myelopoiesis (TAM)-a pre-leukemic state preceding the progression to ML-DS. Read More

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Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice.

Sci Rep 2021 Feb 15;11(1):3847. Epub 2021 Feb 15.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.

Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0-30 mg/kg/day between E7. Read More

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February 2021

Clinical features of 35 Down syndrome patients with transient abnormal myelopoiesis at a single institution.

Int J Hematol 2021 May 4;113(5):662-667. Epub 2021 Jan 4.

Department of Hematology/Oncology, Gunma Children's Medical Center, Shibukawa, Gunma, Japan.

Transient abnormal myelopoiesis (TAM) is a unique clonal myeloproliferation characterized by immature megakaryoblasts that occurs in 5-10% of neonates with Down syndrome (DS). Although TAM regresses spontaneously in most patients, approximately 20% of TAM cases result in early death, and approximately 20% of survivors develop acute megakaryoblastic leukemia (AMKL). We retrospectively reviewed records of 35 DS patients with TAM to determine the correlation between clinical characteristics and blast percentage. Read More

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Transient expansion of TP53 mutated clones in polycythemia vera patients treated with idasanutlin.

Blood Adv 2020 11;4(22):5735-5744

Division of Hematology/Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

Activation of the P53 pathway through inhibition of MDM2 using nutlins has shown clinical promise in the treatment of solid tumors and hematologic malignancies. There is concern, however, that nutlin therapy might stimulate the emergence or expansion of TP53-mutated subclones. We recently published the results of a phase 1 trial of idasanutlin in patients with polycythemia vera (PV) that revealed tolerability and clinical activity. Read More

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November 2020

Complex intracranial vascular complications caused by essential thrombocythemia: a critical case report.

BMC Neurol 2020 Nov 7;20(1):407. Epub 2020 Nov 7.

Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.

Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by elevated and dysfunctional platelets. ET can result in systemic thrombotic and hemorrhagic complications, and it's a rare cause of stroke. The coexistence of multiple vascular lesions has seldom been reported in patients with essential thrombocythemia. Read More

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November 2020

MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members.

Cell Physiol Biochem 2020 Oct;54(5):994-1012

Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca, Romania,

Background/aims: Down syndrome associated disorders are caused by a complex genetic context where trisomy 21 is a central component in relation to other changes involving epigenetic regulators and signaling molecules. This unique genetic context is responsible for the predisposition of people with Down syndrome to acute leukemia. Although, the research in this field has discovered some important pathogenic keys, the exact mechanism of this predisposition is not known. Read More

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October 2020

Comment on: Clinical, cytogenetic, and molecular analyses of 17 neonates with transient abnormal myelopoiesis and nonconstitutional trisomy 21.

Pediatr Blood Cancer 2020 11 29;67(11):e28289. Epub 2020 Jul 29.

Division of Hematology, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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November 2020

Complete blood count differences in a cohort of Down syndrome neonates with transient abnormal myelopoiesis screened for GATA1 pathogenic variants.

Am J Med Genet A 2020 09 18;182(9):2085-2093. Epub 2020 Jul 18.

University of Guadalajara, Health Sciences University Center, Department of Molecular Biology and Genomics, 'Dr. Enrique Corona Rivera' Institute of Human Genetics, Guadalajara, Jalisco, Mexico.

Transient abnormal myelopoiesis (TAM) raises the risk for acute myeloid leukemia of Down syndrome (DS) (ML-DS), and both are related to GATA1 pathogenic variants. Here, we analyzed which findings on complete blood count (CBC) are associated with TAM in a cohort of neonates with DS screened for GATA1 pathogenic variants. The CBCs were compared among 70 newborns with DS, including 16 patients (22. Read More

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September 2020

Ph myeloproliferative neoplasms and the related risk factors for stroke occurrence: Results from a registry of patients treated with Anagrelide.

J Thromb Thrombolysis 2021 Jan;51(1):112-119

University Hospital Hradec Králové, Charles University, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic.

Arterial thrombosis is a common complication in patients with Ph myeloproliferative neoplasms (MPN). We searched for the risk factors of stroke in MPN patients from anagrelide registry. We analyzed the potential risk factors triggering a stroke/TIA event in 249 MPN patients with previous stroke (n = 168) or Transient Ischemic Attack (TIA) (n = 140), and in 1,193 MPN control subjects (without clinical history of thrombosis). Read More

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January 2021

Oncogenic Gata1 causes stage-specific megakaryocyte differentiation delay.

Haematologica 2021 04 1;106(4):1106-1119. Epub 2021 Apr 1.

MRC Molecular Haematology Unit WIMM, University of Oxford, UK.

The megakaryocyte/erythroid Transient Myeloproliferative Disorder (TMD) in newborns with Down Syndrome (DS) occurs when N-terminal truncating mutations of the hemopoietic transcription factor GATA1, that produce GATA1short protein (GATA1s), are acquired early in development. Prior work has shown that murine GATA1s, by itself, causes a transient yolk sac myeloproliferative disorder. However, it is unclear where in the hemopoietic cellular hierarchy GATA1s exerts its effects to produce this myeloproliferative state. Read More

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Transient Myeloproliferative Disorder: A Cytogenomic Update.

J Assoc Genet Technol 2020 ;46(2):74-91

The International Circle of Genetic Studies, Los Angeles, CA.

Objectives: Transient myeloproliferative disorder (TMD), now more commonly known as transient abnormal myelopoiesis (TAM), is a condition closely associated with Down syndrome. Ninety-five percent of Down syndrome cases occur as a result of chromosomal nondisjunction and are rarely due to mosaicism or translocation. TMD is found exclusively in neonates and is most commonly characterized by trisomy 21, somatic GATA1 mutation, and the increased presence of megakaryoblasts. Read More

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January 2020

Transient Abnormal Myelopoeisis and Mosaic Down Syndrome in a Phenotypically Normal Newborn.

Children (Basel) 2020 May 28;7(6). Epub 2020 May 28.

Department of Hematology-Oncology, Texas Children's Hospital, Houston, TX 77030, USA.

Transient abnormal myelopoiesis (TAM) is a common and potentially fatal neonatal complication of newborn babies with Down syndrome (DS). Children born with mosaic DS are also at risk of developing TAM. However, due to their variable phenotypes, early identification of patients with mosaic DS may be difficult; thus, early diagnosis of TAM is just as challenging. Read More

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JAK2 inhibition in JAK2-bearing leukemia cells enriches CD34 leukemic stem cells that are abolished by the telomerase inhibitor GRN163L.

Biochem Biophys Res Commun 2020 06 22;527(2):425-431. Epub 2020 Apr 22.

Department of Medicine, Division of Hematology, Center for Molecular Medicine (CMM) and Bioclinicum, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.

The activating-mutation of JAK2V617F drives the development of myeloproliferative neoplasms (MPNs). Several JAK2 inhibitors such as ruxolitinib and gandotinib (LY2784544) currently in clinical trials and, provide improvements in MPNs including myelofibrosis. However, JAK2 inhibitors are non-curative and murine experiments show that JAK2 inhibitors don't eradicate MPN stem cells and it is currently unclear how they escape. Read More

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Response to tyrosine kinase inhibitors in myeloid neoplasms associated with PCM1-JAK2, BCR-JAK2 and ETV6-ABL1 fusion genes.

Am J Hematol 2020 07 28;95(7):824-833. Epub 2020 Apr 28.

Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany.

We report on 18 patients with myeloid neoplasms and associated tyrosine kinase (TK) fusion genes on treatment with the TK inhibitors (TKI) ruxolitinib (PCM1-JAK2, n = 8; BCR-JAK2, n = 1) and imatinib, nilotinib or dasatinib (ETV6-ABL1, n = 9). On ruxolitinib (median 24 months, range 2-36 months), a complete hematologic response (CHR) and complete cytogenetic response (CCR) was achieved by five of nine and two of nine patients, respectively. However, ruxolitinib was stopped in eight of nine patients because of primary resistance (n = 3), progression (n = 3) or planned allogeneic stem cell transplantation (allo SCT, n = 2). Read More

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Changes in megakaryopoiesis over ontogeny and their implications in health and disease.

Platelets 2020 Aug 21;31(6):692-699. Epub 2020 Mar 21.

Division of Newborn Medicine, Boston Children's Hospital and Harvard Medical School , Boston, MA, USA.

A growing body of research has made it increasingly clear that there are substantial biological differences between fetal/neonatal and adult megakaryopoiesis. Over the last decade, studies revealed a developmentally unique uncoupling of proliferation, polyploidization, and cytoplasmic maturation in neonatal MKs that results in the production of large numbers of small, low ploidy, but mature MKs during this period of development, and identified substantial molecular differences between fetal/neonatal and adult MKs. This review will summarize our current knowledge on the developmental differences between fetal/neonatal and adult MKs, and recent advances in our understanding of the underlying molecular mechanisms, including newly described developmentally regulated pathways and miRNAs. Read More

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Factors influencing platelet normalization of transient abnormal myelopoiesis.

Pediatr Int 2020 Aug 9;62(8):907-910. Epub 2020 Jul 9.

Division of Neonatology, Kanagawa Children's Medical Center, Yokohama, Japan.

Background: Abnormal blood cell counts are characteristic of patients with Down syndrome and transient abnormal myelopoiesis (TAM). Although some patients with TAM experience prolonged anemia or thrombocytopenia, hematological factors predicting blood cell count recovery have not been reported yet. The aim of this study was to investigate the factors influencing platelet normalization in TAM. Read More

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Clinical, cytogenetic, and molecular analyses of 17 neonates with transient abnormal myelopoiesis and nonconstitutional trisomy 21.

Pediatr Blood Cancer 2020 04 5;67(4):e28188. Epub 2020 Feb 5.

Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

Background: Transient abnormal myelopoiesis (TAM) is a unique myeloproliferative disorder that occurs in neonates with constitutional trisomy 21/Down syndrome (DS). Although TAM also develops in neonates without constitutional trisomy 21, the clinical, cytogenetic, and molecular characteristics of those patients are not fully understood.

Procedure: We retrospectively evaluated the clinical and cytogenetic findings and GATA1 mutation status of 17 neonates with TAM and nonconstitutional trisomy 21 tested for GATA1 mutations at our institute, and compared the findings with those of 64 neonates with TAM and constitutional trisomy 21/DS. Read More

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A retrospective study of myeloid leukaemia in children with Down syndrome in Ireland.

Ir J Med Sci 2020 Aug 31;189(3):979-984. Epub 2020 Jan 31.

Department of Haematology and Oncology, Children's Health Ireland at Crumlin, Dublin, Ireland.

Background: Acute megakaryoblastic leukaemia (AMKL) is a subtype of myeloid leukaemia and is the most common leukaemia type in children with Down syndrome (DS) under 4 years of age. AMKL is often preceded by a transient neonatal pre-leukaemic syndrome, transient myeloproliferative disorder (TMD). Although TMD often spontaneously resolves, 20-30% of these patients subsequently develop AMKL within the first 4 years of life. Read More

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Hyperviscosity-related splenic infarction, gastrointestinal ischaemia-reperfusion injury and transient dysarthria in a patient with distributive shock due to idiopathic systemic capillary leak syndrome (Clarkson's syndrome).

BMJ Case Rep 2020 Jan 23;13(1). Epub 2020 Jan 23.

Department of Internal Medicine, Spaarne Gasthuis Medical Centre, Hoofddorp, The Netherlands

Clarkson's syndrome, also known as idiopathic systemic capillary leak syndrome, is characterised by vascular hyperpermeability resulting in intravascular hypovolaemia and shock. A clinician should consider the diagnosis if other causes of shock, for example, sepsis and anaphylaxis, are ruled out and concomitant hyperviscosity is not caused by a myeloproliferative disease. Here, we describe a patient presenting with severe plasma leakage and assumable blood hyperviscosity leading to splenic infarction, gastrointestinal ischaemia-reperfusion syndrome and transient dysarthria. Read More

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January 2020

A Case of Novel GATA-1 Mutation-positive Transient Abnormal Myelopoiesis With Life-threatening Complications in a Neonate With Down Syndrome.

J Pediatr Hematol Oncol 2021 03;43(2):e292-e295

Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, Punjab, India.

Transient abnormal myelopoiesis is a transient myeloproliferative disorder seen in ∼15% to 20% of infants with Down syndrome. These infants are usually asymptomatic, requiring only monitoring, but they can have variable severity of symptoms up to multisystemic dysfunction requiring chemotherapy. GATA-1 somatic mutations acquired in utero are pathognomic of this entity and present nearly in all cases. Read More

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Phosphoproteomic Landscaping Identifies Non-canonical cKIT Signaling in Polycythemia Vera Erythroid Progenitors.

Front Oncol 2019 22;9:1245. Epub 2019 Nov 22.

Myeloproliferative Neoplasm Research Consortium, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Although stem cell factor (SCF)/cKIT interaction plays key functions in erythropoiesis, cKIT signaling in human erythroid cells is still poorly defined. To provide new insights into cKIT-mediated erythroid expansion in development and disease, we performed phosphoproteomic profiling of primary erythroid progenitors from adult blood (AB), cord blood (CB), and Polycythemia Vera (PV) at steady-state and upon SCF stimulation. While AB and CB, respectively, activated transient or sustained canonical cKIT-signaling, PV showed a non-canonical signaling including increased mTOR and ERK1 and decreased DEPTOR. Read More

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November 2019

Spontaneous resolution of transient abnormal myelopoiesis between 34 and 40 weeks gestation.

Br J Haematol 2020 02 8;188(4):481. Epub 2019 Dec 8.

Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.

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February 2020