(PA-216) The PBX1 Protein Is Substantially Overexpressed in Patients with Multiple Myeloma Exhibiting Chromosomal 1q Gain or Amplification, and It Is Associated with Unfavorable Prognosis

Pre-B cell leukemia factor 1 (PBX1) gene, located at chromosome 1q23.3, is a transcription factor that modulates essential oncogenic pathways in multiple myeloma (MM), serves as a negative prognostic factor, and may function as a therapeutic target.

Methods:   

We conducted a retrospective analysis of PBX1 protein expression in bone marrow (BM) biopsies of MM patients with known chromosome 1 abnormalities (1q21+). The immunohistochemical (IH) staining was performed on 3 μm thick sections from paraffin embedded BM biopsies, utilizing a specific PBX1 clone 4A2 monoclonal antibody (Abnova, Taipei, Taiwan, 1mg/mL, M01). In addition, cytogenetic abnormalities (CA) were assessed using fluorescence in situ hybridization (FISH) on CD138-positive BM plasma cells. FISH analysis and BM IH staining were performed on samples obtained at the same time point. Overall survival (OS) was determined with the Kaplan-Meier method. Fifty-four BM specimens from MM patients were analyzed, comprising 45 individuals with 1q21+ and 9 patients without 1q21+.

Results:   Of the 54 patients, 31 were men (57.4%) and 23 women (42.6%) with a median age at diagnosis of 64 years (range, 42 - 86 years). Disease stage at diagnosis defined by R-ISS was I in 10 (18.5%) patients, II in 23 (42.6%) patients, III in 19 (35.2%) patients, while for 2 (3.7%) patients it was unknown. Regarding the 45 patients with 1q21+, gain or amplification was present in 29 (64.4%) and 13 (28,9%) patients respectively, while for 3 (6.7%) patients it was unknown. Co-existence of other CA was present in 28 (62.2%) patients. Detection of TP53 was found in 10 (22.2%) patients while t(4;14), t(14;16) and t(11;14) were found in 8 (17.7%), 5 (11.1%) and 5 (11.1%) patients respectively. Lactate dehydrogenase (LDH) at diagnosis was elevated in 17 patients (37.8%). PBX1 protein was expressed in 22 (49%) patients with 1q21+, whereas 23 (51%) were negative. Half of the patients with PBX1 positivity had additional CA and disease stage III R-ISS was found in 10 (10/22, 45.5%) of them. Of the 9 patients lacking 1q21+, PBX1 protein was expressed in 2 (2/9, 22.2%) patients. The estimated 5-year OS for the patients who expressed PBX1 was 34.4% (95% CI: 16.2%-72.8%) versus 48.7% (95% CI: 25.8%-91.9%) for PBX1 negative patients (p 0.54).

Conclusions:   The PBX1 protein expression in BM biopsies of MM patients with 1q21+ appears to correlate with a poor trend in overall survival. Further research of the effect of PBX1 expression in the clinical outcome of patients with MM is needed.