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Träfflista för sökning "WFRF:(Kanduri Meena) ;pers:(Staffas Anna)"

Sökning: WFRF:(Kanduri Meena) > Staffas Anna

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1.
  • Schneider, Edith, et al. (författare)
  • MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.
  • 2020
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 34, s. 1253-1265
  • Tidskriftsartikel (refereegranskat)abstract
    • MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation, cell death, and differentiation in many tissues and aberrant Hox gene expression can create a predisposition to leukemogenesis in hematopoietic cells. However, possible linkages between the regulatory pathways of Hox genes and miRNAs are not yet fully resolved. We identified miR-708 to be upregulated in Hoxa9/Meis1 AML inducing cell lines as well as in AML patients. We further showed Meis1 directly targeting miR-708 and modulating its expression through epigenetic transcriptional regulation. CRISPR/Cas9 mediated knockout of miR-708 in Hoxa9/Meis1 cells delayed disease onset in vivo, demonstrating for the first time a pro-leukemic contribution of miR-708 in this context. Overexpression of miR-708 however strongly impeded Hoxa9 mediated transformation and homing capacity in vivo through modulation of adhesion factors and induction of myeloid differentiation. Taken together, we reveal miR-708, a putative tumor suppressor miRNA and direct target of Meis1, as a potent antagonist of the Hoxa9 phenotype but an effector of transformation in Hoxa9/Meis1. This unexpected finding highlights the yet unexplored role of miRNAs as indirect regulators of the Hox program during normal and aberrant hematopoiesis.
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2.
  • Staffas, Anna, 1982, et al. (författare)
  • Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia.
  • 2011
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:22, s. 5905-5913
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutation status of the FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in pediatric AML patients enrolled in the NOPHO 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients respectively. Presence of FLT3-ITD was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of pediatric AML patients and that determination of the BAALC gene expression level can add valuable information.
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  • Resultat 1-3 av 3

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