MPN: The Molecular Drivers of Disease Initiation, Progression and Transformation and their Effect on Treatment

被引：36

作者：

Grabek, Julian ^{[1
,2
]}

Straube, Jasmin ^{[1
,2
]}

Bywater, Megan ^{[1
,2
]}

Lane, Steven W. ^{[1
,2
,3
]}

机构：

[1] QIMR Berghofer Med Res Inst, Canc Program, Brisbane, Qld 4006, Australia

[2] Univ Queensland, Fac Med, Brisbane, Qld 4072, Australia

[3] Royal Brisbane & Womens Hosp, Canc Care Serv, Brisbane, Qld 4029, Australia

来源：

CELLS | 2020年 / 9卷 / 08期

关键词：

MPN; myeloproliferation; JAK2; CALR; MPL; driver mutations; leukemic transformation; IFN alpha; chromatin modifiers; spliceosome; DNA methylation; tumour suppressors; transcriptional regulators; HEMATOPOIETIC STEM-CELLS; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; MYELOPROLIFERATIVE NEOPLASMS; AVAILABLE THERAPY; THROMBOPOIETIN RECEPTOR; LEUKEMIC TRANSFORMATION; PRIMARY MYELOFIBROSIS; MOUSE MODEL;

D O I：

10.3390/cells9081901

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Myeloproliferative neoplasms (MPNs) constitute a group of disorders identified by an overproduction of cells derived from myeloid lineage. The majority of MPNs have an identifiable driver mutation responsible for cytokine-independent proliferative signalling. The acquisition of coexisting mutations in chromatin modifiers, spliceosome complex components, DNA methylation modifiers, tumour suppressors and transcriptional regulators have been identified as major pathways for disease progression and leukemic transformation. They also confer different sensitivities to therapeutic options. This review will explore the molecular basis of MPN pathogenesis and specifically examine the impact of coexisting mutations on disease biology and therapeutic options.

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