Altered Hematopoietic Cell Gene Expression Precedes Development of Therapy-Related Myelodysplasia/Acute Myeloid Leukemia and Identifies Patients at Risk

Academic Article

Abstract

  • Therapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) is a major complication of cancer treatment. We compared gene expression in CD34+ cells from patients who developed t-MDS/AML after autologous hematopoietic cell transplantation (aHCT) for lymphoma with controls who did not develop t-MDS/AML. We observed altered gene expression related to mitochondrial function, metabolism, and hematopoietic regulation in pre-aHCT samples from patients who subsequently developed t-MDS/AML. Progression to overt t-MDS/AML was associated with additional alterations in cell-cycle regulatory genes. An optimal 38-gene PBSC classifier accurately distinguished patients who did or did not develop t-MDS/AML in an independent group of patients. We conclude that genetic programs associated with t-MDS/AML are perturbed long before disease onset, and accurately identify patients at risk for this complication. © 2011 Elsevier Inc.
  • Published In

  • Cancer Cell  Journal
  • Digital Object Identifier (doi)

    Author List

  • Li L; Li M; Sun C; Francisco L; Chakraborty S; Sabado M; McDonald T; Gyorffy J; Chang K; Wang S
  • Start Page

  • 591
  • End Page

  • 605
  • Volume

  • 20
  • Issue

  • 5