Figure 5

FANCD2 expression predicts poor survival in a subset of patients with newly diagnosed multiple myeloma. (A) FANCD2 mRNA levels (gene probe ID 242560) in normal bone marrow (BM) plasma cells (NPC, green), “premalignant” BM plasma cells from individuals with monoclonal gammopathy of undetermined significance (MGUS, purple) or malignant plasma cells from patients with multiple myeloma (MM, black). (B) Reduced event-free survival (EFS) and overall survival (OS) in myeloma patients with elevated FANCD2 levels (log-rank analysis). Of 351 patients, 175 and 176 patients were arbitrarily categorized as “Low FANCD2” and “High FANCD2,” respectively, using the median FANCD2 level in this cohort as cut-off. EFS and OS data were available from 129 (37%) and 85 (24%) patients, respectively. (C) Proportion of myelomas (n = 351) that fell into 8 different subgroups of the disease based on cytogenetic features (e.g., ploidy and chromosomal translocations) and molecular genetic features (e.g., gene expression signatures). From top to bottom, the following subgroups are distinguished: MF, MAF/MAFB; CD1, CCND1/CCND3 group 1; PR, proliferation; LB, low bone disease; CD2, CCND1/CCND3 group 2; MS, MMSET; HY, hyperdiploid; MY, myeloid [39]. The distribution of standard-risk (blue) and high-risk cases (red) according to the 70-gene signature [18] is also indicated. (D) Shown to the left is elevation of FANCD2 message in high-risk myeloma (red) vs. standard-risk myeloma (blue) in 4 of 8 subgroups of the disease included in panel C. Mean values (microarray units) and standard error of the mean (SEM) are plotted. Mann–Whitney tests were used for statistical analyses (n. s., not significant). Shown to the right is the increase in FANCD2 mRNA in high-risk disease (red; 13%) vs. standard-risk disease (blue; 87%) in 351 myeloma patients. Mean values and SEM are plotted. Median FANCD2 levels in high-risk and standard-risk disease were 473 and 269, respectively.