Overexpression of CD49f in Precursor B-Cell Acute Lymphoblastic Leukemia: Efficiency of Minimal Residual Disease (MRD) Detection by Flow Cytometric Immunophenotyping Compared with Commonly Used Markers
H Shinoda-Matsuoka, JA DiGiuseppe. Hartford Hospital, Hartford, CT
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 (FCM) requires demonstration of abnormal antigen expression in leukemic B-cell precursors relative to that of normal B-cell precursors (hematogones). We have recently shown that CD49f (integrin alpha-6) is commonly overexpressed in pB-ALL relative to normal B-cell precursors, and represents a potentially useful marker for the immunophenotypic detection of MRD (DiGiuseppe JA, et. al. Cytometry Part B; in press). However, the efficiency of MRD detection using CD49f has not been compared with that of more commonly used markers, such as CD10, CD13, CD33, CD38, and CD58.
Design: We studied a series of 25 patients (median age: 5 years) with pB-ALL in whom residual disease was detectable (i.e., >0.01%) at one or more times following induction chemotherapy. Expression of CD49f, as well as CD10, CD13, CD33, CD38, and CD58, was evaluated by 4-color FCM in bone marrow aspirate samples, and compared with expression of each of these antigens in normal B-cell precursors. In order to be considered abnormal, expression of a given antigen was required to be recognizably distinct from that of normal B-cell precursors by visual inspection of dot plots, with at most minimal overlap in fluorescence intensity.
Results: CD49f was overexpressed in 22 of 25 (88%) cases. The proportion of cases with abnormal CD49f expression was significantly higher than the proportions observed using CD10, CD13, CD38, and CD58 (Table 1); comparison with aberrant CD33 expression approached, but did not reach, statistical significance.
|# of abnormal/ total# of cases||6/25||15/25||16/25||9/25||13/25||22/25|
|% of abnormal cases||24||60||64||36||52||88|
|p value vs. CD49f||<0.01||0.02||0.07||<0.01||0.01||N.A.|
Moreover, in informative cases, the difference in intensity between CD49f expression in leukemic blasts relative to normal B-cell precursors was typically dramatic, facilitating detection of MRD by visual inspection of dot plots.
Conclusions: The efficiency of CD49f overexpression as a marker of MRD in pB-ALL compares favorably with that of markers commonly used in current practice, suggesting that CD49f may be a useful addition to existing antibody panels.
Tuesday, March 10, 2009 1:30 PM
Platform Session: Section G, Tuesday Afternoon