Clinical Significance of YY1 Overexpression in Human Hematopoietic Malignancies

Abstract

Patients with multiple myeloma (MM) develop resistance to conven- tional therapies. The underlying molecular mechanism responsible for resistance is not clear. We have reported in solid tumors that transcription factor Yin Yang 1 (YY1) is overexpressed and regulates tumor cell resistance to apoptotic stimuli induced by chemo- and immunotherapeutic drugs. Therefore, we hypothesized that MM may overexpress YY1 and that its overexpression may be a poor prognostic factor. This hypothesis was tested by using both MM cell lines and MM derived from patients' bone marrow samples. MM cell lines showed overexpression of YY1 by immunohistochemistry (IHC). Bone marrow samples from patients with MM showed overexpression of YY1 by IHC as compared with low levels of YY1 in normal bone marrow samples. The intensity and frequency of cells expressing YY1 in both the cytoplasm and nucleus was significantly higher among patients with progressive disease compared with patients with stable and responsive dis- ease. These findings demonstrate that the expression of YY1 in MM may correlate with prognosis. Furthermore, the findings suggest YY1 as a therapeutic target for intervention in the reversal of resistance and prevention of disease progression in patients with MM.