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Full Article-PDF K.B. Kotade et al, IJCTPR, 2015, 3(3): 924–931 ISSN: 2321-3760 International Journal of Current Trends in Pharmaceutical Research Journal Home Page: www.pharmaresearchlibrary.com/ijctpr Review Article Open Access A Review on Myeloproliferative disorder K.B. Kotade*1, P.Kadbhane1, S.B Somwanshi2, K.B.Dhamak3 1Department of Pharmacology, P.R.E.S.’s, College of Pharmacy (For Women), Chincholi, Nashik-422 102. 2Department of Pharmaceutics, P.R.E.S.’s, College of Pharmacy (For Women), Chincholi, Nashik-422 102. 3Department of Pharmaceutical Chemistry, P.R.E.S.’s, College of Pharmacy (For Women), Chincholi, Nashik-422 102 A B S T R A C T The term myeloproliferative disorder (MPD) was first introduced by Dr William. Myeloproliferative disorder is the general name given to a group of conditions where there is an overgrowth of cells in the bone marrow, often leading to increased number of cells in the blood. Myeloproliferative disorders are described according to the blood cell which is most affected. There are four types of myeloproliferative disorder that together represent around 95% of all cases. Polycythemia Vera (PV), Essential thrombocythemia (ET), Primary or idiopathic myelofibrosis (PMF), Chronic myelogenous leukemia (CML). Uncommon types of myeloproliferative disorder together make up about 5% of cases are chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), Mastocytosis. MPD can be diagnosed by using a combination of laboratory tests and a physical examination. The treatment or combination of treatment chosen will depend on several factor including the duration and severity of disorder, whether or not you have a history of blood clots, age and general health. A mutation of a gene known as jenus kinase (JAK 2) is found in large proportion of people with myeloproliferative disorder. The discovery of mutation in JAK2 gene is important because it has significant impact on the way myeloproliferative disorder are diagnosed and may be important for treatment in the future. Keywords: Bone marrow, Jenus kinase, Leukemia, Mutation, Myeloproliferative disorder (MPD). A R T I C L E I N F O CONTENTS 1. Introduction . 925 2. Causes of Myelopriliferative Disorder. 925 3. Types of Chronic Myrloproliferative Disorder . 926 4. Conclusion . .. .. .931 5. References . .931 Article History: Received Accepted Available Online 27 February 2015, 29 March 2015, 15 May 2015 *Corresponding Author K.B. Kotade Department of Pharmacology, P.R.E.S.’s, College of Pharmacy (For Women), Chincholi, Nashik-422102. Manuscript ID: IJCTPR2525 PAPER-QR CODE Citation: Int. J. Curnt. Tren. Pharm, Res. K.B. Kotade, et al. A Review on Myeloproliferative disorder. , 2015, 3(3): 924-931. International Journal of Current Trends in Pharmaceutical Research 924 K.B. Kotade et al, IJCTPR, 2015, 3(3): 924–931 ISSN: 2321-3760 Copyright © 2015 K.B. Kotade, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is 1.properly Introduction cited. The term myeloproliferative disorder (MPD) was first The JAK2 V617F Mutation: introduced by Dr William in 1951 to emphasize the In 2005, several groups reported a single, acquired point clinicopathological similarities between chronic myeloid mutation in the Janus kinase 2 (JAK2) genes in the majority leukemia (CML), essential thrombocythemia (ET), of patients with Ph-negative myeloproliferative disorders. polycythemia vera (PV), and with myeloid metaplsia JAK2, a cytoplasmic tyrosine kinas, is critical for (MMM).Accordingly, these four disorders are currently instigating intracellular signaling by the receptors for referred as “classic MPD”. Myeloproliferative disorders are erythropoietin, thrombopoietin, interleukin-3, granulocyte diseases in which too many of certain types of blood cells - colony-stimulating factor (G-CSF), and granulocyte– monocytes, platelets, fibroblasts, red blood cells -are made macrophage colony-stimulating factor (GMCSF). Mice that in the bone marrow, the spongy tissue inside the large are deficient in Jak2 die at embryonic day 12.5, with a bones in the body where red and white blood cells and complete absence of definitive erythropoiesis, a finding that platelets are made.The chronic myeloproliferative disorders underscores the vital role of JAK2 as a transducer of signals (MPD) are a group of related diseases that are characterized evoked by the binding of erythropoietin to its receptor. by neoplastic proliferation in one or more hematopoietic JAK2 binds to the erythropoietin receptor in the cell lines. Myeloproliferative disorder is the general name endoplasmic reticulum and is required for its cell-surface given to a group of conditions where there is an overgrowth expression. When erythropoietin binds to its receptor, it of cells in the bone marrow, often leading to increased provokes a conformational change in the receptor with number of cells in the blood. In myeloproliferative disorder consequent phosphorylation and activation of JAK2.63 the the cells in bone marrow multiply in an uncontrolled way. activated JAK2 then phosphorylates the receptor’s In contrast with leukemia, where there is an overgrowth of cytoplasmic domain, thereby promoting the docking of immature cells. In myeloproliferative disorders the cells downstream effector proteins and the initiation of mature with normal function, there are just too many of intracellular signaling cascades. them. It is important to remember, that myeloproliferative disorder are chronic disease that, in most cases, remain The JAK2 mutation in the myeloproliferative disorders is stable for many years and progress gradually overtime [1]. not in the germ line but, rather, is acquired. Sensitive methods demonstrate the mutation in more than 95% of The cause of myeloproliferative disorder remains unknown, patients with polycythemia Vera and in 50 to 60% of although there is now rapidly increasing knowledge of patients with essential thrombocythemia or idiopathic some of the changes that trigger the disease. myelofibrosis. A substantial proportion of patients with Myeloproliferative disorders are sometime described as polycythemia vera or idiopathic myelofibrosis are being clonal blood stem cell disorder. This means that result homozygous for the JAK2 mutation as a result of mitotic from a change, or mutation, in DNA of single blood stem recombination affecting chromosome 9p, 6-9 but this cells. This change (or changes) results in abnormal blood phenomenon is rarely detected in essential cell development, and in this case, the overproduction of thrombocythemia. The mutation is also found in a small blood cells.In myeloproliferative disorders the original minority of patients with the hypereosinophilic syndrome, mutation is preserved when the affected stem cells divided chronic myelomonocytic leukemia, chronic neutrophilic (proliferates) and produces a ‘clone’ a group of identical leukemia, myelodysplatic, or acute myeloid leukemia, but stem cells all with the same defect. Mutation in dividing not in patients with lymphoid or other cancers or in those cells occur all the time and cells have sophisticated without hematologic disorders. The presence of a mutant mechanisms within them to stop these abnormalities JAK2 in some patients with acute myeloid leukemia, persisting. A mutation of a gene known as jenus kinase especially older patients, raises the possibility that they may (JAK 2) is found in large proportion of people with have had a preceding, undiagnosed myeloproliferative myeloproliferative disorder. The discovery of mutation in disorder [3]. JAK2 gene is important because it has significant impact Screening Tests: on the way myeloproliferative disorder are diagnosed and Several laboratory methods of JAK2V617F mutation may be important for treatment in the future. Finally, detection are currently available, and one must interpret test myeloproliferative disorder are not contagious; we cannot results in the context of assay sensitivity. For example, in catch these disorders by being in contact with a one of the first reports on JAK2V617F, mutational myeloproliferative disorder have no family history of these frequency in PV increased from 73% to 97% by using an disease. The longer we live, more chance we have acquiring allele-specific PCR assay (~3% sensitivity) as compared to mutations that escape these safeguards. That’s why direct sequencing (~20% sensitivity). On the other hand, myeloproliferative disorder can become more common as false positive results could arise from the utilization of ultra we get older [2]. sensitive assay systems (~0.01% sensitivity) that could detect very low levels of JAK2V617F even in healthy 2. Causes of Myelopriliferative Disorder: individuals. In general, quantitative PCR methods are International Journal of Current Trends in Pharmaceutical Research 925 K.B. Kotade et al, IJCTPR, 2015, 3(3): 924–931 ISSN: 2321-3760 preferred because of their potential value in measuring 2. Chronic eosinophilic leukemia (CEL). mutant allele burden and monitoring treatment response. 3. Mastocytosis[1]. Conventional DNA sequencing 4.1 Polycythemia Vere: A PCR amplified DNA sequence of interest (in this Introduction of PV: instance the mutated DNA region of JAK2) is processed Polycythemia Vera (PV) is a myeloproliferative disorder through an automated sequencer that is based on the Sanger characterized by overproduction of red blood cell (RBC) DNA sequencing principle.
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