Abstract:
:The JAK2 V617F mutation is present in the majority of patients with a myeloproliferative neoplasm (MPN) and is sufficient to recapitulate an MPN in murine models. However, the consequences of JAK2 mutations for myeloid differentiation are poorly understood. After systematic analyses of a large cohort of JAK2-mutated MPN patients, we demonstrate in vivo that JAK2 mutations do not alter hematopoietic stem and progenitor cell com-partment size or in vitro behavior but generate expansion of later myeloid differentiation compartments, where homozygous expression of the mutation confers an added proliferative advantage at the single-cell level. In addition, we demonstrate that these findings may be partially explained by the expression pattern of JAK2, which markedly increases on myeloid differentiation. Our findings have potential clinical relevance, as they predict that JAK2 inhibitors may control myeloproliferation, but may have limited efficacy in eradicating the leukemic stem cells that sustain the human MPN.
journal_name
Bloodjournal_title
Bloodauthors
Anand S,Stedham F,Beer P,Gudgin E,Ortmann CA,Bench A,Erber W,Green AR,Huntly BJdoi
10.1182/blood-2010-12-327593subject
Has Abstractpub_date
2011-07-07 00:00:00pages
177-81issue
1eissn
0006-4971issn
1528-0020pii
blood-2010-12-327593journal_volume
118pub_type
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