Genetic–pathologic characterization of myeloproliferative neoplasms.
- Author:
Yonggoo KIM
1
;
Joonhong PARK
;
Irene JO
;
Gun Dong LEE
;
Jiyeon KIM
;
Ahlm KWON
;
Hayoung CHOI
;
Woori JANG
;
Hyojin CHAE
;
Kyungja HAN
;
Ki Seong EOM
;
Byung Sik CHO
;
Sung Eun LEE
;
Jinyoung YANG
;
Seung Hwan SHIN
;
Hyunjung KIM
;
Yoon Ho KO
;
Haeil PARK
;
Jong Youl JIN
;
Seungok LEE
;
Dong Wook JEKARL
;
Seung Ah YAHNG
;
Myungshin KIM
Author Information
- Publication Type:Original Article
- MeSH: Alleles; Bone Marrow; Chromosome Aberrations; Disease Progression; Fibrosis; Hematopoietic Stem Cells; Humans; Hyperplasia; Prognosis; Prospective Studies
- From:Experimental & Molecular Medicine 2016;48(7):e247-
- CountryRepublic of Korea
- Language:English
- Abstract: 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 ⩾2) 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.
