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KMID : 0620920160480070003
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Experimental & Molecular Medicine
2016 Volume.48 No. 7 p.3 ~ p.3
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Genetic?pathologic characterization of myeloproliferative neoplasms
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Kim Yong-Goo
Park Joon-Hong
Jo Irene
Lee Gun-Dong
Kim Ji-Yeon
Kwon A-hlm
Choi Ha-Young
Jang Woo-Ri
Chae Hyo-Jin
Han Kyung-Ja
Eom Ki-Seong
Cho Byung-Sik
Lee Sung-Eun
Yang Jin-Young
Shin Seung-Hwan
Kim Hyun-Jung
Ko Yoon-Ho
Park Hae-Il
Jin Jong-Youl
Lee Seung-Ok
Jekarl Dong-Wook
Yahng Seung-Ah
Kim Myung-Shin
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Abstract
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Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages. The current study demonstrates that three driver mutations were detected in 82.6% of 407 MPNs with a mutation distribution of JAK2 in 275 (67.6%), CALR in 55 (13.5%) and MPL in 6 (1.5%). The mutations were mutually exclusive in principle except in one patient with both CALR and MPL mutations. The driver mutation directed the pathologic features of MPNs, including lineage hyperplasia, laboratory findings and clinical presentation. JAK2-mutated MPN showed erythroid, granulocytic and/or megakaryocytic hyperplasia whereas CALR- and MPL-mutated MPNs displayed granulocytic and/or megakaryocytic hyperplasia. The lineage hyperplasia was closely associated with a higher mutant allele burden and peripheral cytosis. These findings corroborated that the lineage hyperplasia consisted of clonal proliferation of each hematopoietic lineage acquiring driver mutations. Our study has also demonstrated that bone marrow (BM) fibrosis was associated with disease progression. Patients with overt fibrosis (grade greater than or equal to2) presented an increased mutant allele burden (P<0.001), an increase in chromosomal abnormalities (P<0.001) and a poor prognosis (P<0.001). Moreover, among patients with overt fibrosis, all patients with wild-type JAK2/CALR/MPL (triple-negative) showed genomic alterations by genome-wide microarray study and revealed the poorest overall survival, followed by JAK2-mutated MPNs. The genetic?pathologic characteristics provided the information for understanding disease pathogenesis and the progression of MPNs. The prognostic significance of the driver mutation and BM fibrosis suggests the necessity of a prospective therapeutic strategy to improve the clinical outcome.
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KEYWORD
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