title: Enhanced leukemia cell detection using a novel magnetic needle and nanoparticles.
abstract: Acute leukemia is a hematopoietic malignancy for which the accurate measurement of minimal residual disease is critical to determining prognosis and treatment. Although bone marrow aspiration and light microscopy remain the current standard of care for detecting residual disease, these approaches cannot reliably discriminate less than 5% lymphoblast cells. To improve the detection of leukemia cells in the marrow, we developed a novel apparatus that utilizes antibodies conjugated to superparamagnetic iron oxide nanoparticles (SPION) and directed against the acute leukemia antigen CD34, coupled with a "magnetic needle" biopsy. Leukemia cell lines expressing high or minimal CD34 were incubated with anti-CD34-conjugated SPIONs. Three separate approaches including microscopy, superconducting quantum interference device magnetometry, and in vitro magnetic needle extraction were then used to assess cell sampling. We found that CD34-conjugated nanoparticles preferentially bind high CD34-expressing cell lines. Furthermore, the magnetic needle enabled identification of both cell line and patient leukemia cells diluted into normal blood at concentrations below those normally found in remission marrow samples. Finally, the magnetic needle enhanced the percentage of lymphoblasts detectable by light microscopy by 10-fold in samples of fresh bone marrow aspirate approximating minimal residual disease. These data suggest that bone marrow biopsy using antigen-targeted magnetic nanoparticles and a magnetic needle for the evaluation of minimal residual disease in CD34-positive acute leukemias can significantly enhance sensitivity compared with the current standard of care.
authors.affiliation: Department of Pathology, University of New Mexico and Cancer Research and Treatment Center, Albuquerque, New Mexico 87131, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Jaetao
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Butler
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Adolphi
authors.forename: Debbie M
authors.initials: DM
authors.lastname: Lovato
authors.forename: Howard C
authors.initials: HC
authors.lastname: Bryant
authors.forename: Ian
authors.initials: I
authors.lastname: Rabinowitz
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Winter
authors.forename: Trace E
authors.initials: TE
authors.lastname: Tessier
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Hathaway
authors.forename: Christian
authors.initials: C
authors.lastname: Bergemann
authors.forename: Edward R
authors.initials: ER
authors.lastname: Flynn
authors.forename: Richard S
authors.initials: RS
authors.lastname: Larson
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis*; D001854:Bone Marrow Cells / Q000473:pathology*; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D007938:Leukemia / Q000175:diagnosis*; D008280:Magnetics; D053768:Metal Nanoparticles; D018365:Neoplasm, Residual / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
chemical_list: D018952:Antigens, CD34; D005290:Ferric Compounds; C000499:ferric oxide