Upregulation of FOXM1 in a subset of relapsed myeloma results in poor outcome

Article: Upregulation of FOXM1 in a subset of relapsed myeloma results in poor outcome

Authors: Chunyan Gu, Carol Holman, Ramakrishna Sompallae, Xuefang Jing, Michael Tomasson, Dirk Hose, Anja Seckinger, Fenghuang Zhan, Guido Tricot, Hartmut Goldschmidt, Ye Yang, and Siegfried Janz

Journal: Blood Cancer J. 2018 Feb 15;8(2):22

Following up on our previous work demonstrating the involvement of the transcription factor, forkhead box M1 (FOXM1), in the biology and outcome of a high-risk subset of newly diagnosed multiple myeloma (nMM)1, we sought to determine whether upregulation of FOXM1 may also be a feature of relapsed myeloma (rMM). To that end, we analyzed the total therapy 2 (TT2) dataset (GSE2658) from the University of Arkansas for Medical Science, which contains microarray-based gene expression and clinical outcome data on 88 patients with known FOXM1 mRNA levels at baseline and relapse. Statistical comparison demonstrated a significant increase (p = 10−4) in mean (by ~70%) and median (~2.9-fold) FOXM1 expression upon relapse (Fig. ​(Fig.1a,1a, left). Just like in nMM1, the distinction between high and low FOXM1 message at relapse was of prognostic value: FOXM1High patients (n = 11, 12.5%) exhibited markedly reduced event-free survival and overall survival compared to FOXM1Low patients (n = 77, Fig. ​Fig.1a,1a, right). To confirm these results with the help of an independent dataset that is more recent than TT2, we took advantage of myeloma patients from the University of Heidelberg, Germany, which were uniformly treated upfront using HDT/ASCT and new myeloma drugs. In this cohort of 692 patients with nMM, FOXM1High status was as negative a predictor of survival (Fig. ​(Fig.1b)1b) as in the original study.

Link to journal online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814454/

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