FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2955758900> ?p ?o ?g. }

• W2955758900 abstract "The myeloproliferative neoplasms (MPNs) are stem cell disorders characterized by hematopoietic stem cell (HSC) expansion and an increased propensity to develop hematologic malignancies. The acquired kinase mutation JAK2V617F plays a central role in MPNs. In this work we tested the hypothesis that the JAK2V617F-bearing megakaryocytes (MKs), an important component of the hematopoietic niche, promotes HSC dysfunction in MPNs. Methods JAK2V617F Flip-Flop (FF1) mice and Pf4-Cre mice (Radek Skoda, Switzerland) were crossed to generate MK lineage-specific human JAK2V617F knock-in mouse line (Pf4/FF1). Animal experiments were performed in accordance with the Institutional Animal Care and Use Committee guideline. Results We previously reported that, at 28 wks of age, the Pf4/FF1 mice developed a murine myeloproliferative syndrome with moderate thrombocytosis, splenomegaly, increased marrow MKs, and a 3-fold increase of CD45+CD201+CD150+CD48- HSCs with increased donor engraftment in a competitive repopulation assay compared to Pf4-cre control mice. (Zhan Leukemia 2016; Zhang Stem Cells 2018) Rigorous, extremely sensitive RT-PCR assays eliminated the possibility that HSCs in Pf4/FF1 mice express the mutant kinase. To study the effect of JAK2V617F-bearing MKs on HSC function during aging, we followed the Pf4/FF1 mice up to 2 years of age. At 2 yr, there were significant neutrophilia in Pf4/FF1 mice but no change was observed in hemoglobin, platelet count, or marrow HSC cell numbers compared to age-matched control mice. Indeed, while HSC numbers significantly increased in old (2-yr) control mice compared to young (6-mo) control mice (3.3-fold, p=0.0002, n=4-8), there was no significant increase of HSCs between old and young Pf4/FF1 mice (1.6-fold, p=0.158, n=6-8). A competitive marrow transplantation experiment was performed in which CD45.2 donor marrow cells from 2-yr old Pf4/FF1 or control mice were injected intravenously together with competitor CD45.1 wild-type marrow cells intro lethally irradiated wild-type recipient (CD45.1) (n=8-9 in each group). During a 4-month follow up, old HSCs from the Pf4/FF1 mice displayed hallmarks of murine hematopoietic aging including a lower peripheral blood donor chimerism, increased myeloid blood cell production, and decreased lymphoid cells compared to old HSCs from control mice. To begin to understand how JAK2V617F-bearing MKs promote the aging phenotype of HSCs in old Pf4/FF1 mice, qRT-PCR of purified HSCs identified up-regulation of p21 (2-fold, p = 0.019) in Pf4/FF1 mice compared to controls. Conclusion The Pf4/FF1 mice, in which the JAK2V617F expression is restricted to MKs, developed a myeloproliferative phenotype at young age and accelerated stem cell aging at old age. The precise mechanism by which JAK2V617F-bearing MKs affect the MPN marrow niche and stem cell dysfunction during disease progression deserve further investigation. Citation Format: Helen Wong, Melissa Castiglione, Molly Quan, Huichun Zhan. JAK2V617F-mutant megakaryocytes contribute to stem cell aging in myeloproliferative neoplasms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1172." @default.
• W2955758900 created "2019-07-12" @default.
• W2955758900 creator A5016156042 @default.
• W2955758900 creator A5023463201 @default.
• W2955758900 creator A5027960601 @default.
• W2955758900 creator A5084981601 @default.
• W2955758900 date "2019-07-01" @default.
• W2955758900 modified "2023-09-24" @default.
• W2955758900 title "Abstract 1172: JAK2V617F-mutant megakaryocytes contribute to stem cell aging in myeloproliferative neoplasms" @default.
• W2955758900 doi "https://doi.org/10.1158/1538-7445.sabcs18-1172" @default.
• W2955758900 hasPublicationYear "2019" @default.
• W2955758900 type Work @default.
• W2955758900 sameAs 2955758900 @default.
• W2955758900 citedByCount "0" @default.
• W2955758900 crossrefType "proceedings-article" @default.
• W2955758900 hasAuthorship W2955758900A5016156042 @default.
• W2955758900 hasAuthorship W2955758900A5023463201 @default.
• W2955758900 hasAuthorship W2955758900A5027960601 @default.
• W2955758900 hasAuthorship W2955758900A5084981601 @default.
• W2955758900 hasBestOaLocation W29557589001 @default.
• W2955758900 hasConcept C109159458 @default.
• W2955758900 hasConcept C201750760 @default.
• W2955758900 hasConcept C203014093 @default.
• W2955758900 hasConcept C2778086970 @default.
• W2955758900 hasConcept C2779705218 @default.
• W2955758900 hasConcept C28328180 @default.
• W2955758900 hasConcept C502942594 @default.
• W2955758900 hasConcept C71924100 @default.
• W2955758900 hasConcept C86803240 @default.
• W2955758900 hasConcept C95444343 @default.
• W2955758900 hasConcept C98274493 @default.
• W2955758900 hasConceptScore W2955758900C109159458 @default.
• W2955758900 hasConceptScore W2955758900C201750760 @default.
• W2955758900 hasConceptScore W2955758900C203014093 @default.
• W2955758900 hasConceptScore W2955758900C2778086970 @default.
• W2955758900 hasConceptScore W2955758900C2779705218 @default.
• W2955758900 hasConceptScore W2955758900C28328180 @default.
• W2955758900 hasConceptScore W2955758900C502942594 @default.
• W2955758900 hasConceptScore W2955758900C71924100 @default.
• W2955758900 hasConceptScore W2955758900C86803240 @default.
• W2955758900 hasConceptScore W2955758900C95444343 @default.
• W2955758900 hasConceptScore W2955758900C98274493 @default.
• W2955758900 hasLocation W29557589001 @default.
• W2955758900 hasOpenAccess W2955758900 @default.
• W2955758900 hasPrimaryLocation W29557589001 @default.
• W2955758900 hasRelatedWork W2005479110 @default.
• W2955758900 hasRelatedWork W2101255241 @default.
• W2955758900 hasRelatedWork W2148479228 @default.
• W2955758900 hasRelatedWork W2511976864 @default.
• W2955758900 hasRelatedWork W2549594786 @default.
• W2955758900 hasRelatedWork W2554424937 @default.
• W2955758900 hasRelatedWork W2554472954 @default.
• W2955758900 hasRelatedWork W2555105507 @default.
• W2955758900 hasRelatedWork W2562952524 @default.
• W2955758900 hasRelatedWork W2574266820 @default.
• W2955758900 hasRelatedWork W2574855891 @default.
• W2955758900 hasRelatedWork W2588483108 @default.
• W2955758900 hasRelatedWork W2613220561 @default.
• W2955758900 hasRelatedWork W2784199188 @default.
• W2955758900 hasRelatedWork W2979449469 @default.
• W2955758900 hasRelatedWork W2981023329 @default.
• W2955758900 hasRelatedWork W2986346627 @default.
• W2955758900 hasRelatedWork W2986517167 @default.
• W2955758900 hasRelatedWork W2987716874 @default.
• W2955758900 hasRelatedWork W2993518707 @default.
• W2955758900 isParatext "false" @default.
• W2955758900 isRetracted "false" @default.
• W2955758900 magId "2955758900" @default.
• W2955758900 workType "article" @default.