Pathway-specific apoptotic gene expression profiling in chronic lymphocytic leukemia and follicular lymphoma.
Defects in the apoptotic pathway are pathogenetically important in chronic lymphocytic leukemia and follicular lymphoma. To further understand these defects, we profiled the apoptotic gene expression of these two neoplasms. Oligonucleotide arrays with 112 apoptotic genes were used, and data analysis was performed on seven chronic lymphocytic leukemia and 10 follicular lymphoma frozen tumor samples from six and seven patients, respectively. The overall gene expression pattern was strikingly similar among all 17 samples, regardless of the type of lymphoma and history of chemotherapy exposure. MCL1, TNFRSF1B and TNFRSF7 were highly expressed in most cases. The apoptotic gene expression between the groups of untreated chronic lymphocytic leukemia (n=3) and untreated follicular lymphoma (n=6) was also similar (Pearson correlation coefficient, 0.94). Comparison between the groups of untreated chronic lymphocytic leukemia (n=3) and postchemotherapy chronic lymphocytic leukemia (n=4) revealed six genes with >2-fold changes, including BIRC5/Survivin that was higher in the postchemotherapy samples. This finding was validated by immunohistochemistry. Similar analysis of follicular lymphoma cases did not identify any significant differences. To conclude, our findings suggest that chronic lymphocytic leukemia and follicular lymphoma share common apoptotic defects, and highlight the importance of MCL1 and the TNF pathway. Upregulation of survivin may be one of the mechanisms by which chronic lymphocytic leukemia becomes desensitized to chemotherapy.
Hui
David
D
Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AL, Canada.
Satkunam
Natasha
N
Al Kaptan
Moayad
M
Reiman
Tony
T
Lai
Raymond
R
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics*; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II; D000077022:Survivin; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D000077022:Survivin; C415902:TNFRSF1B protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7