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Gene expression pattern of ESPL1, PTTG1 and PTTG1IP can potentially predict response to TKI first-line treatment of patients with newly diagnosed CML

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The achievement of major molecular response (MMR, BCR::ABL1 ≤ 0.1% IS) within the first year of treatment with tyrosine kinase inhibitors (TKI) is a milestone in the therapeutic management of patients with newly diagnosed chronic myeloid leukemia (CML). We analyzed the predictive value of gene expre...

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Main Authors: Christiani, Eva (Author) , Naumann, Nicole (Author) , Weiß, Christel (Author) , Spiess, Birgit (Author) , Kleiner, Helga (Author) , Fabarius, Alice (Author) , Hofmann, Wolf-Karsten (Author) , Saußele, Susanne (Author) , Seifarth, Wolfgang (Author)
Format: Article (Journal)
Language:English
Published: 8 May 2023
In: Cancers
Year: 2023, Volume: 15, Issue: 9, Pages: 1-17
ISSN:2072-6694
DOI:10.3390/cancers15092652
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers15092652
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/15/9/2652
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Author Notes:Eva Christiani, Nicole Naumann, Christel Weiss, Birgit Spiess, Helga Kleiner, Alice Fabarius, Wolf-Karsten Hofmann, Susanne Saussele and Wolfgang Seifarth

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520 |a The achievement of major molecular response (MMR, BCR::ABL1 ≤ 0.1% IS) within the first year of treatment with tyrosine kinase inhibitors (TKI) is a milestone in the therapeutic management of patients with newly diagnosed chronic myeloid leukemia (CML). We analyzed the predictive value of gene expression levels of ESPL1/Separase, PTTG1/Securin and PTTG1IP/Securin interacting protein for MMR achievement within 12 months. Relative expression levels (normalized to GUSB) of ESPL1, PTTG1 and PTTG1IP in white blood cells of patients (responders n = 46, non-responders n = 51) at the time of diagnosis were comparatively analyzed by qRT-PCR. 3D scatter plot analysis combined with a distance analysis performed with respect to a commonly calculated centroid center resulted in a trend to larger distances for non-responders compared to the responder cohort (p = 0.0187). Logistic regression and analysis of maximum likelihood estimates revealed a positive correlation of distance (cut-off) with non-achieving MMR within 12 months (p = 0.0388, odds ratio 1.479, 95%CI: 1.020 to 2.143). Thus, 10% of the tested non-responders (cut-off ≥ 5.9) could have been predicted already at the time of diagnosis. Future scoring of ESPL1, PTTG1 and PTTG1IP transcript levels may be a helpful tool in risk stratification of CML patients before initiation of TKI first-line treatment. 
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