title: New markers for minimal residual disease detection in acute lymphoblastic leukemia.
abstract: To identify new markers for minimal residual disease (MRD) detection in acute lymphoblastic leukemia (ALL), we compared genome-wide gene expression of lymphoblasts from 270 patients with newly diagnosed childhood ALL to that of normal CD19⁺CD10⁺ B-cell progenitors (n = 4). Expression of 30 genes differentially expressed by ≥ 3-fold in at least 25% of cases of ALL (or 40% of ALL subtypes) was tested by flow cytometry in 200 B-lineage ALL and 61 nonleukemic BM samples, including samples containing hematogones. Of the 30 markers, 22 (CD44, BCL2, HSPB1, CD73, CD24, CD123, CD72, CD86, CD200, CD79b, CD164, CD304, CD97, CD102, CD99, CD300a, CD130, PBX1, CTNNA1, ITGB7, CD69, CD49f) were differentially expressed in up to 81.4% of ALL cases; expression of some markers was associated with the presence of genetic abnormalities. Results of MRD detection by flow cytometry with these markers correlated well with those of molecular testing (52 follow-up samples from 18 patients); sequential studies during treatment and diagnosis-relapse comparisons documented their stability. When incorporated in 6-marker combinations, the new markers afforded the detection of 1 leukemic cell among 10(5) BM cells. These new markers should allow MRD studies in all B-lineage ALL patients, and substantially improve their sensitivity.
authors.affiliation: Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Coustan-Smith
authors.forename: Guangchun
authors.initials: G
authors.lastname: Song
authors.forename: Christopher
authors.initials: C
authors.lastname: Clark
authors.forename: Laura
authors.initials: L
authors.lastname: Key
authors.forename: Peixin
authors.initials: P
authors.lastname: Liu
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mehrpooya
authors.forename: Patricia
authors.initials: P
authors.lastname: Stow
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Su
authors.forename: Sheila
authors.initials: S
authors.lastname: Shurtleff
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: James R
authors.initials: JR
authors.lastname: Downing
authors.forename: Dario
authors.initials: D
authors.lastname: Campana
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000628:therapy; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor