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Among B-cell precursor acute lymphoblastic leukemia (B-ALL), t(9;22) (q34;q11) responsible for BCR/ABL fusion transcripts is the most common cytogenetic abnormality that occurs in around 20-30% of adult patients (pts). BCR/ABL-positive (BCR/ABL+) B-ALL has been typically associated with high expression of myeloid antigen such as CD13, CD33, CD66c. We analyzed 44 adult patients with B-ALL diagnosed in our center from December 2004 to December 2013, with a median age of 46 ys (range 13-78), 23 males and 21 females.

The purpose of this study was to establish by immunophenotyping which combination of antigens was most predictive for BCR/ABL gene rearrangement.

Flow-cytometric data were acquired by immunophenotypic B-ALL definition panels performed using FACSCanto cytometer and BDFACSCanto software. Arbitrary cutoff of 20% analyzed events that were brighter than the control stain, was required for an antigen to be considered positive. Levels of BCR-ABL fusion transcript were quantified in RT-PCR assay. Comparison between two groups were performed using the Mann–Whitney U (MWW) and Chi-square tests (CSQ) or Fisher exact test (FET) for continuous and dichotomic variables, respectively. Measure of association was expressed by Odds Ratio (OR). Cut-off value for the marker was selected using receiver operating curves (ROC). Multivariate analysis was performed using Logistic Regression (LR). P values lower than 0.05 were considered  statistically significant (SPSS 15.0 version).

BCR/ABL transcript was identified in 21 pts (47.7%). CD10 and CD34 was positive in the totality of BCR/ABL+ cases. BCR/ABL+ pts exhibited a greater median percentage of CD10 (96.8% vs 88.6%, MWW, P = 0.030) and CD34 (98.3% vs 92.3%, MWW, P = 0.013) expressions, but a lower median percentage of CD38 expression (92.6% vs 99.0%, MWW, P = 0.001) than pts with BCR/ABL-. Considering Median Fluorescence Intensity (MFI), BCR/ABL+ cases presented a higher CD10 MFI (median of MFI, 11295 vs 1972, MWW, P = 0.001) and a lower CD38 MFI (median of MFI, 919 vs 6747, MWW, P = 0.006) than their counterpart. No significant difference were observed in CD34 MFI values comparison. By calculating ROC, the best cut-off for CD10 MFI was 5159 (AUC = 0.787, 95% CI: from 0.65 to 0.92) and for CD38 MFI was 6284 (AUC = 0.750, 95% CI: from 0.60 to 0.90). These cut-off values provided a sensitivity of 80% and a specificity of 74% for CD10 and a sensitivity of 83% and a specificity of 54% for CD38. Categorized CD10 MFI and CD38 MFI presented a strong association with BCR/ABL rearrangement [CSQ, P < 0.001, OR 12.75 (95% CI: from 3.06 to 53.19); P = 0.010, OR 0.14 (95% CI: from 0.03 to 0.59), respectively]. CD66c positivity was more frequent in BCR/ABL+ pts than in the others (81% vs 45%, FET, P = 0.016). The co-expression of CD66c with CD13 or CD33 was more frequently present in BCR/ABL+ pts (44% and 39%, respectively) than in BCR/ABL- (13% and 6%, respectively)(FET, P = 0.04). The sensitivity and the specificity of CD66c as sole marker were 81% and 55%, respectively. In opposite, the co-expression of CD66c/CD13 or CD66c/CD33 showed a lower sensitivity (44% and 39%, respectively) and a greater specificity (88% and 94%, respectively). Multivariate analysis in which categorized CD10 MFI was combined with categorized CD38 MFI and CD66c expression showed that CD10 was an independent predictor for the presence of BCR/ABL rearrangement (LR, P = 0.003).

We suggest a screening panel predictive for BCR/ABL rearrangement in B-ALL by using the combination of CD38, CD10, CD34, CD66c, CD13 and CD33 expressions.