title: In situ RHAMM protein expression in acute myeloid leukemia blasts suggests poor overall survival.
abstract: Treatment options for patients with high-risk acute myeloid leukemia (AML) include high-dose chemotherapy regimens in combination with allogeneic hematopoietic stem cell transplantation, which takes advantage of the donor T-cell-mediated graft-versus-leukemia effect. Together with beneficial responses observed in assays targeted at leukemia-associated antigens (LAA), this encouraged research on cancer vaccines and adoptive cellular therapies in AML. The receptor for hyaluronic acid-mediated motility (RHAMM, CD168) was identified as one of the most promising LAA in AML. Thus far, little is known about in situ expression in leukemic bone marrow blasts or the prognostic role of RHAMM and its interaction partners in AML. We immunohistochemically analyzed the expression and prognostic significance of RHAMM on trephine bone marrow biopsies from 71 AML cases that had been evaluated for cytogenetics and presence of FLT3-internal tandem duplications and NPM1 mutations. Fifty-five patients (77%) were treated with curative intent, while 16 (23%) received the most appropriate supportive care. Twenty of 71 (28%) AML cases were considered RHAMM+. Receiver operating characteristic curves showed significant discriminatory power considering overall survival (OS) in AML patients treated curatively for RHAMM (p = 0.015). Multivariable analysis revealed that expression of RHAMM in >5% of leukemic blasts identifies a subgroup of curatively treated cases with adverse OS independent of failures to achieve complete remission. RHAMM not only represents a promising LAA with specific T-cell responses in AML but, if assessed in situ on blasts, also a probable prognostic factor.
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland. atzankov@uhbs.ch
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.forename: Ulrich
authors.initials: U
authors.lastname: Strasser
authors.forename: Stephan
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: Thomas
authors.initials: T
authors.lastname: Menter
authors.forename: Caroline
authors.initials: C
authors.lastname: Arber
authors.forename: Martine
authors.initials: M
authors.lastname: Jotterand
authors.forename: Alicia
authors.initials: A
authors.lastname: Rovo
authors.forename: Andre
authors.initials: A
authors.lastname: Tichelli
authors.forename: Reinhard
authors.initials: R
authors.lastname: Stauder
authors.forename: Ursula
authors.initials: U
authors.lastname: Günthert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001752:Blast Crisis / Q000473:pathology; D001856:Bone Marrow Examination; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000090243:Nucleophosmin; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C000716967:NPM1 protein, human; C098946:hyaluronan-mediated motility receptor; D000090243:Nucleophosmin