Low Socioeconomic Status, Adverse Gene Expression Profiles, and Clinical Outcomes in Hematopoietic Stem Cell Transplant Recipients.
OBJECTIVE
Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biologic mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA), which involves upregulation of proinflammatory genes and downregulation of genes involved in type I IFN response and antibody synthesis.


METHODS
We compared pretransplant leukocyte CTRA gene expression between a group of 78 high versus low SES recipients of unrelated donor HCT for acute myelogenous leukemia in first remission. Post hoc exploratory analyses also evaluated whether CTRA gene expression was associated with poor clinical outcomes.


RESULTS
Peripheral blood mononuclear cells collected pre-HCT from low SES individuals demonstrated significant CTRA upregulation compared with matched HCT recipients of high SES. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity, including increased CREB signaling and decreased IRF and GR signaling. High expression of the CTRA gene profile was also associated with increased relapse risk and decreased leukemia-free survival.


CONCLUSIONS
Low SES is associated with increased expression of the CTRA gene profile, and CTRA gene expression is associated with adverse HCT clinical outcomes. These findings provide a biologic framework within which to understand how social environmental conditions may influence immune function and clinical outcomes in allogeneic HCT.
Medical College of Wisconsin, Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. jmknight@mcw.edu.
Jennifer M
JM
Knight
Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
J Douglas
JD
Rizzo
Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
Brent R
BR
Logan
Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
Tao
T
Wang
Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles, Los Angeles, California.
Jesusa M G
JM
Arevalo
Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles, Los Angeles, California.
Jeffrey
J
Ma
Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles, Los Angeles, California.
Steve W
SW
Cole
D000328:Adult; D002423:Cause of Death; D015897:Comorbidity; D005260:Female; D020869:Gene Expression Profiling; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D063868:Patient Outcome Assessment; D011379:Prognosis; D012042:Registries; D012307:Risk Factors; D012923:Social Class; D014019:Tissue Donors; D059467:Transcriptome; D055815:Young Adult