title: Levels of soluble HLA-I and beta2M in patients with acute myeloid leukemia and advanced myelodysplastic syndrome: association with clinical behavior and outcome of induction therapy.
abstract: beta-2 Microglobulin (beta2M), a subunit of human leukocyte antigen-class I (HLA-I), is well established as a marker of prognosis in various solid tumors and hematologic malignancies. The prognostic role of intact free-circulating HLA-I (sHLA-I) is less well understood. We compared the clinical relevance of plasma levels of sHLA-I and beta2M in patients with acute myeloid leukemia (AML; n=209) or advanced myelodysplastic syndrome (MDS; n=98). sHLA-1 and beta2M levels were significantly higher in AML and MDS patients than in control subjects, but did not differ significantly between the two disease groups. In AML patients, multivariate analysis showed both sHLA-1 and beta2-M to be highly predictive of complete remission (CR), survival and duration of complete response (CRD). In MDS, the predictive value of the two markers differed substantially from one another: beta2M was associated with survival, CR and CRD, whereas sHLA-I was not. These findings not only establish the role of sHLA-I as a tumor marker in AML but also support that MDS is clinically and biologically distinct from AML. sHLA-I has been reported to be an immunomodulator inhibiting the cytotoxic effects of T-lymphocytes, which may offset its predictive value for disease aggressiveness in patients with MDS.
authors.affiliation: Department of Hematopathology, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92690, USA. maher.x.albitar@questdiagnostics.com
authors.forename: M
authors.initials: M
authors.lastname: Albitar
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: K A
authors.initials: KA
authors.lastname: Do
authors.forename: A
authors.initials: A
authors.lastname: Day
authors.forename: I
authors.initials: I
authors.lastname: Jilani
authors.forename: S
authors.initials: S
authors.lastname: Pierce
authors.forename: E
authors.initials: E
authors.lastname: Estey
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: M
authors.initials: M
authors.lastname: Keating
authors.forename: S
authors.initials: S
authors.lastname: Verstovsek
authors.forename: S
authors.initials: S
authors.lastname: O'brien
authors.forename: F J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D003561:Cytarabine / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006680:HLA Antigens / Q000097:blood*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D009363:Neoplasm Proteins / Q000097:blood*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012074:Remission Induction; D012995:Solubility; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D001613:beta 2-Microglobulin / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D006680:HLA Antigens; D009363:Neoplasm Proteins; D001613:beta 2-Microglobulin; D003561:Cytarabine; D019772:Topotecan; D014740:Vidarabine; C024352:fludarabine; D015255:Idarubicin