Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: potential usefulness in minimal residual disease detection.
BACKGROUND
The persistence of minimal residual disease (MRD) following therapy is an established prognostic factor in precursor B-cell acute lymphoblastic leukemia (pB-ALL). Detection of MRD in pB-ALL by flow cytometric immunophenotyping requires demonstration of abnormal antigen expression in leukemic B-cell precursors relative to that of normal B-cell precursors. The gene encoding CD49f (integrin alpha-6) is one of several whose overexpression in pB-ALL at diagnosis has been associated with the subsequent detection of MRD. However, whether CD49f might be a useful reagent in the immunophenotypic detection of MRD in pB-ALL has not been evaluated.


METHODS
We evaluated CD49f expression by 4-color flow cytometry in normal B-cell precursors, and in a series of cases of pB-ALL, both at diagnosis and at intervals following the initiation of therapy.


RESULTS
In 10 control marrow samples, CD49f was undetectable or extremely dim in all but a minor subset of normal CD19+ B-lineage cells, whereas in 11 of 15 cases (73%) of pB-ALL, CD49f was moderate or bright at diagnosis, and persisted or became brighter after initiation of therapy. MRD detected using CD49f corresponded precisely with that obtained using a standard panel of antibodies, and permitted the detection of leukemic populations comprising as little as 0.02% of cells. Of the four pB-ALL cases in which CD49f was undetectable or dim at diagnosis, MRD was detected in two; in one of these, CD49f expression was substantially increased in the leukemic cells that persisted following initiation of therapy.


CONCLUSIONS
CD49f is commonly overexpressed in p-B-ALL, and represents a potentially useful marker for the immunophenotypic detection of MRD.
DiGiuseppe
Joseph A
JA
Department of Pathology and Laboratory Medicine, Hartford Hospital, Connecticut 06102-5037, USA. jdigius@harthosp.org
Fuller
Sheila G
SG
Borowitz
Michael J
MJ
D000293:Adolescent; D000367:Age Factors; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007223:Infant; D039503:Integrin alpha6 / Q000032:analysis* / Q000097:blood*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D055815:Young Adult
D015415:Biomarkers; D039503:Integrin alpha6