Identification of a novel human gene, ZFP91, involved in acute myelogenous leukemia.
To elucidate mechanisms leading to acute myelogenous leukemia (AML), to find sensitive markers and novel targets for drug therapy, and to allow choice of suitable chemotherapy for each affected individual, we previously compared expression of mRNA from mononuclear cells of AML patients with that of normal controls using a cDNA microarray. Data from that study identified many genes that were commonly up- or down-regulated in AML cells. Of these, we report here the identification of a novel gene whose expression was increased in 27 (93%) of the 29 AML cases whose PBMC preparations include >70% leukemia cells. The gene product, localized in nuclei, showed several characteristics of transcription factors: five zinc-finger domains, a leucine zipper, and several nuclear localization signals. Its 92.5% identity in amino-acid sequence to the murine penta zinc finger protein (mPZf; gene symbol Zfp91), led us to term it ZFP91. Anti-sense oligonucleotides inhibited expression of ZFP91, suppressed cell growth, and induced apoptosis. Our results suggest that ZFP91 is likely to play an important role in cell proliferation and/or anti-apoptosis, and may serve as a molecular marker for AML.
Unoki
Motoko
M
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Okutsu
Junichi
J
Nakamura
Yusuke
Y
D000595:Amino Acid Sequence; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000032:analysis; D001752:Blast Crisis; D001854:Bone Marrow Cells / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000235:genetics / Q000473:pathology; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016335:Zinc Fingers
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; C096797:ZNF91 protein, human