High PARP1 expression is correlated with poor survival in MM. (A) Box plot displaying PARP1 mRNA range of expression (Affymetrix probe 208644_at) according to the molecular subgroup in a cohort of MM patients from the Arkansas dataset (GSE4581). Note the higher PARP1 expression in the MR, MS, and PR subgroups. (B) Kaplan-Meier overall survival curves of MM patients treated in total therapy 1 and 3 according to PARP1 mRNA expression above or below the median value of 5025 (left panel) or according to the quartiles distribution (right panel) of PARP1 mRNA expression based on National Institutes of Health GEO dataset deposited by Dr J. D. Shaughnessy Jr under accession number GSE4581. Quartile 4 represents the subgroup with the highest PARP1 expression. The 60-month OS for patients with PARP1 below and above the median are 67% and 54%, respectively (P = .02). (C-D) Myeloma tissue microarray constructed from the BM biopsies of 83 newly diagnosed MM patients was used to evaluate the expression of PARP1 by immunofluorescence staining and its impact on prognosis. Shown are representative histospots with low and high AQUA score for PARP1 expression, respectively, in panels C and D. AQUA scores are calculated based on the average PARP1 signal intensity per compartment area (CD138+ cells) of 3 representative histospots per patient (detailed methodology for AQUA score calculation is provided in supplemental Methods). Staining for DAPI, CD138, and PARP1 is merged together in the figure. (E) Kaplan-Meier survival curves indicate the shorter time to progression (TTP) and overall survival (OS) for patients with MM cells expressing high protein levels of PARP1.