Diagnosis, prognosis and identification of potential therapeutic targets of multiple myeloma based on gene expression profiling
Gene expression profiling is a powerful tool that has varied utility. It enables classification of multiple myeloma into subtypes and identifying genes directly involved in disease pathogenesis and clinical manifestation. The present invention used gene expression profiling in large uniformly treated population of patients with myeloma to identify genes associated with poor prognosis. It also demonstrated that over-expression of CKS1B gene, mainly due to gene amplification that was determined by Fluorescent in-situ hybridization to impart a poor prognosis in multiple myleoma. It is further contemplated that therapeutic strategies that directly target CKS1B or related pathways may represent novel, and more specific means of treating high risk myeloma and may prevent its secondary evolution.
1. A method of identifying a human subject having an aggressive form of multiple myeloma, comprising the steps of:
obtaining a bone marrow sample from the subject;
binding a probe to a chromosome in cells of said subject sample;
binding the probe to the chromosome in cells of a control sample;
detecting via fluorescent in situ hybridization a signal from the probe upon binding to a locus of said chromosome in the subject sample and a signal from the probe upon binding to the locus of said chromosome in the control sample; and
determining, from the detected signals, an amplification of CKS1B gene on chromosome 1q21, or a deletion of AHCYL1 gene on chromosome 1p13, wherein amplification of the 1q21 gene or deletion of the 1p13 gene in the subject sample compared to the control sample indicates the human subject has the aggressive form of multiple myeloma.
2. The method of claim 1 , wherein said fluorescent in situ hybridization comprises interphase fluorescent in situ hybridization, metaphase fluorescent in situ hybridization, or both.
3. A method of treating a human subject having an aggressive form of multiple myeloma identified by the method of claim 1 , comprising the step of:
administering an effective amount of bortezomib to the human subject.
4. The method of claim 1 , further comprising:
determining loss of a D13S31/RB1 gene on 13q14 or loss of a D13S285 gene on 13qtel.