title: Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk.
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.
authors.affiliation: City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Canlan
authors.initials: C
authors.lastname: Sun
authors.forename: Liton
authors.initials: L
authors.lastname: Francisco
authors.forename: Sujata
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Melanie
authors.initials: M
authors.lastname: Sabado
authors.forename: Tinisha
authors.initials: T
authors.lastname: McDonald
authors.forename: Janelle
authors.initials: J
authors.lastname: Gyorffy
authors.forename: Karen
authors.initials: K
authors.lastname: Chang
authors.forename: Shirong
authors.initials: S
authors.lastname: Wang
authors.forename: Wenhong
authors.initials: W
authors.lastname: Fan
authors.forename: Jiangning
authors.initials: J
authors.lastname: Li
authors.forename: Lue Ping
authors.initials: LP
authors.lastname: Zhao
authors.forename: Jerald
authors.initials: J
authors.lastname: Radich
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
authors.forename: Ravi
authors.initials: R
authors.lastname: Bhatia
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D015331:Cohort Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008928:Mitochondria / Q000502:physiology; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012307:Risk Factors
chemical_list: D018952:Antigens, CD34
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