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Blood, 1 April 2001, Vol. 97, No. 7, pp. 2115-2120
NEOPLASIA
Identification of novel markers for monitoring minimal residual
disease in acute lymphoblastic leukemia
Jiann-Shiuh Chen,
Elaine Coustan-Smith,
Toshio Suzuki,
Geoffrey A. Neale,
Keichiro Mihara,
Ching-Hon Pui, and
Dario Campana
From the Departments of Hematology-Oncology and
Pathology, St Jude Children's Research Hospital, Memphis, TN; and
University of Tennessee College of Medicine, Memphis.
To identify new markers of minimal residual disease (MRD) in
B-lineage acute lymphoblastic leukemia (ALL), gene expression of
leukemic cells obtained from 4 patients with newly diagnosed ALL was compared with that of
normal CD19+CD10+ B-cell progenitors
obtained from 2 healthy donors. By cDNA array analysis, 334 of 4132 genes studied were expressed 1.5- to 5.8-fold higher in leukemic cells
relative to both normal samples; 238 of these genes were also
overexpressed in the leukemic cell line RS4;11. Nine genes were
selected among the 274 overexpressed in at least 2 leukemic samples,
and expression of the encoded proteins was measured by flow cytometry.
Two proteins (caldesmon and myeloid nuclear differentiation antigen)
were only weakly expressed in leukemic cells despite strong
hybridization signals in the array. By contrast, 7 proteins (CD58,
creatine kinase B, ninjurin1, Ref1, calpastatin, HDJ-2, and annexin VI)
were expressed in B-lineage ALL cells at higher levels than in normal
CD19+CD10+ B-cell progenitors
(P < .05 in all comparisons). CD58 was chosen for
further analysis because of its abundant and prevalent
overexpression. An anti-CD58 antibody identified residual
leukemic cells (0.01% to 1.13%; median, 0.03%) in 9 of 104 bone
marrow samples from children with ALL in clinical remission. MRD
estimates by CD58 staining correlated well with those of polymerase
chain reaction amplification of immunoglobulin genes. These results
indicate that studies of gene expression with cDNA arrays can aid the
discovery of leukemia markers.
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