Transcriptosome and serum cytokine profiling of an atypical case of myelodysplastic syndrome with progression to acute myelogenous leukemia

Daruka Mahadevan, Johanna DiMento, Kimiko Della Croce, Christopher Riley, Benjamin George, Deborah Fuchs, Timothy Mathews, Charlton Wilson, Michael Lobell

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 ∼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), proliferate 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.

Original languageEnglish (US)
Pages (from-to)779-786
Number of pages8
JournalAmerican Journal of Hematology
Volume81
Issue number10
DOIs
StatePublished - Oct 2006
Externally publishedYes

Keywords

  • Anemia
  • Refractory anemia
  • Thrombocytosis

ASJC Scopus subject areas

  • Hematology

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