Gene Expression Pattern of ESPL1, PTTG1 and PTTG1IP Can Potentially Predict Response to TKI First-Line Treatment of Patients with Newly Diagnosed CML

Eva Christiani; Nicole Naumann; Christel Weiss; Birgit Spiess; Helga Kleiner; Alice Fabarius; Wolf-Karsten Hofmann; Susanne Saussele; Wolfgang Seifarth

doi:10.3390/cancers15092652

Gene Expression Pattern of ESPL1, PTTG1 and PTTG1IP Can Potentially Predict Response to TKI First-Line Treatment of Patients with Newly Diagnosed CML

Cancers (Basel). 2023 May 8;15(9):2652. doi: 10.3390/cancers15092652.

Authors

Eva Christiani¹, Nicole Naumann¹, Christel Weiss², Birgit Spiess¹, Helga Kleiner¹, Alice Fabarius¹, Wolf-Karsten Hofmann¹, Susanne Saussele¹, Wolfgang Seifarth¹

Affiliations

¹ Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
² Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.

Abstract

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.

Keywords: BCR::ABL1 expression; ESPL1/Separase; PTTG1/Securin; PTTG1IP/Securin interacting protein; TKI first-line treatment; chronic myeloid leukemia (CML); major molecular response (MMR); risk stratification at initial diagnosis.

Abstract

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