Transcriptosome and serum cytokine profiling of an atypical case of myelodysplastic syndrome with progression to acute myelogenous leukemia.
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.
Mahadevan
Daruka
D
University of Arizona Cancer Center, Tucson, Arizona 85724, USA. dmahadevan@azcc.arizona.edu
DiMento
Johanna
J
Croce
Kimiko Della
KD
Riley
Christopher
C
George
Benjamin
B
Fuchs
Deborah
D
Mathews
Timothy
T
Wilson
Charlton
C
Lobell
Michael
M
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
D014408:Biomarkers, Tumor; D016207:Cytokines; D018970:Insulin-Like Growth Factor Binding Protein 1; D017228:Hepatocyte Growth Factor