title: High expression of suppressor of cytokine signaling-2 predicts poor outcome in pediatric acute myeloid leukemia: a report from the Children's Oncology Group.
abstract: Deregulated cytokine signaling is a characteristic feature of acute myeloid leukemia (AML), and expression signatures of cytokines and chemokines have been identified as a significant prognostic factor in this disease. Given this aberrant signaling, we hypothesized that expression of suppressor of cytokine signaling-2 (SOCS2), a negative regulator of cytokine signaling, might be altered in AML and could provide predictive information. Among 188 participants of the Children's Oncology Group AAML03P1 trial, SOCS2 mRNA levels varied > 6000-fold. Higher (> median) SOCS2 expression was associated with inferior overall (60 ± 10% vs. 75 ± 9%, p = 0.026) and event-free (44 ± 10% vs. 59 ± 10%, p = 0.031) survival. However, these differences were accounted for by higher prevalence of high-risk and lower prevalence of low-risk disease among patients with higher SOCS2 expression, limiting the clinical utility of SOCS2 as a predictive marker. It remains untested whether high SOCS2 expression identifies a subset of leukemias with deregulated cytokine signaling that could be amenable to therapeutic intervention.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center , Seattle, WA , USA.
authors.forename: George S
authors.initials: GS
authors.lastname: Laszlo
authors.forename: Rhonda E
authors.initials: RE
authors.lastname: Ries
authors.forename: Chelsea J
authors.initials: CJ
authors.lastname: Gudgeon
authors.forename: Kimberly H
authors.initials: KH
authors.lastname: Harrington
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: Betsy A
authors.initials: BA
authors.lastname: Hirsch
authors.forename: Alan S
authors.initials: AS
authors.lastname: Gamis
authors.forename: Soheil
authors.initials: S
authors.lastname: Meshinchi
authors.forename: Roland B
authors.initials: RB
authors.lastname: Walter
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D018365:Neoplasm, Residual; D010865:Pilot Projects; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012008:Recurrence; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C106643:SOCS2 protein, human; D050826:Suppressor of Cytokine Signaling Proteins
keywords: SOCS2; acute myeloid leukemia; childhood cancer; cytokine; prognostic factor