title: Transcriptosome and serum cytokine profiling of an atypical case of myelodysplastic syndrome with progression to acute myelogenous leukemia.
abstract: A Native American-Indian female presenting with anemia and thrombocytosis was diagnosed with myelodysplastic syndrome (MDS, refractory anemia). Over the course of 5 years she developed cytopenias and periods of leukocytosis with normal bone marrow (BM) blast counts, features of an unclassifiable MDS/MPS syndrome. The patient ultimately progressed to acute myelogenous leukemia (AML, FAB M2) and had a normal karyotype throughout her course. The episodes of leukocytosis were associated with infectious complications. Transformation to AML was characterized by a BM blast percentage of 49%. Peripheral blood and BM samples were obtained for serum protein analysis and gene expression profiling (GEP) to elucidate her disease process. An ELISA assay of the serum analyzed approximately 80 cytokines, which demonstrated that hepatocyte growth factor/scatter factor and insulin-like growth factor binding protein 1 were markedly elevated compared to normal. GEP demonstrated a unique "tumor molecular profile," which included overexpression of oncogenes (HOXA9, N-MYC, KOC1), proliferative genes (PAWR, DLG5, AKR1C3), invasion/metastatic genes (FN1, N-CAM-1, ITGB5), pro-angiogenesis genes (c-Kit), and down regulation of tumor suppressor genes (SUI1, BARD1) and anti-apoptotic genes (PGLYRP, SERPINB2, MPO). Hence, a biomics approach has provided insight into elucidating disease mechanisms, molecular prognostic factors, and discovery of novel targets for therapeutic intervention.
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona 85724, USA. dmahadevan@azcc.arizona.edu
authors.forename: Daruka
authors.initials: D
authors.lastname: Mahadevan
authors.forename: Johanna
authors.initials: J
authors.lastname: DiMento
authors.forename: Kimiko Della
authors.initials: KD
authors.lastname: Croce
authors.forename: Christopher
authors.initials: C
authors.lastname: Riley
authors.forename: Benjamin
authors.initials: B
authors.lastname: George
authors.forename: Deborah
authors.initials: D
authors.lastname: Fuchs
authors.forename: Timothy
authors.initials: T
authors.lastname: Mathews
authors.forename: Charlton
authors.initials: C
authors.lastname: Wilson
authors.forename: Michael
authors.initials: M
authors.lastname: Lobell
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D017809:Fatal Outcome; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D018970:Insulin-Like Growth Factor Binding Protein 1; D017228:Hepatocyte Growth Factor