B Lymphoblastic Leukemia/lymphoma Research Articles

CD25 Expression in B Lymphoblastic Leukemia/Lymphoma Predicts t(9;22)(q34;q11)/Philadelphia Chromosome Translocation (Ph) and Is Associated With Residual Disease in Ph-Negative Patients.

CD25 expression is associated with t(9;22)(q34;q11)/Philadelphia chromosome translocation (Ph); BCR-ABL1 rearrangement in B lymphoblastic leukemia/lymphoma (B-LL). However, the significance of CD25 expression in Ph negative (Ph-) B-LL regarding residual disease (RD) and genetic abnormalities is largely unknown. CD25 expression by flow cytometry (FC) was correlated with Ph status in 95 newly diagnosed B-LL patients and with RD status in day 29 marrow measured by FC in the context of cytogenetic risk stratification in Ph- patients. CD25 expression was greater in Ph positive (Ph+) patients (80%) than in Ph- patients (17%), predicting Ph+ with 80% sensitivity and 86% specificity. In Ph- patients, CD25 expression (in 14 patients, 16%) was associated with RD in the cytogenetic intermediate-risk group: detectable RD in 50% of CD25+ patients vs 14% of CD25- patients. Interestingly, one CD25+/Ph- patient had a Ph-like genotype ( ZC3HAV1-ABL2 rearrangement), and another had dual MYC-IGH and BCL2-IGH rearrangements. Our findings not only confirm the predictive power of CD25 expression for Ph+ but also demonstrate that CD25 expression is associated with RD (a biomarker correlated with prognosis) in Ph- patients. The latter finding is likely associated with underlying molecular abnormalities, including Ph-like genotype.

B-ALL minimal residual disease flow cytometry: an application of a novel method for optimization of a single-tube model.

Optimizing a clinical flow cytometry panel can be a subjective process dependent on experience. We develop a quantitative method to make this process more rigorous and apply it to B lymphoblastic leukemia/lymphoma (B-ALL) minimal residual disease (MRD) testing. We retrospectively analyzed our existing three-tube, seven-color B-ALL MRD panel and used our novel method to develop an optimized one-tube, eight-color panel, which was tested prospectively. The optimized one-tube, eight-color panel resulted in greater efficiency of time and resources with no loss in diagnostic power. Constructing a flow cytometry panel using a rigorous, objective, quantitative method permits optimization and avoids problems of interdependence and redundancy in a large, multiantigen panel.

B-lymphoblastic leukemia/lymphoma: overexpression of nuclear DNA repair protein PARP-1 correlates with antiapoptotic protein Bcl-2 and complex chromosomal abnormalities.

Poly(ADP-ribose) polymerase-1 (PARP-1) and Bcl-2 are emerging as therapeutic targets in various cancers. The former is a DNA repair protein associated with genomic stability and apoptosis, whereas the latter is an antiapoptotic protein having a DNA repair function through inhibition of PARP-1. Because genomic stability is critical for prognosis in B-lymphoblastic leukemia/lymphoma (B-ALL), we studied the expression of PARP-1 and Bcl-2 proteins in patients with B-ALL of different ages and compared the results with cytogenetic data. The PARP-1 protein was overexpressed in about two-thirds (61%) of patients with B-ALL. It had a nuclear location, whereas Bcl-2 protein was cytosolic. Expression of the 2 proteins showed a highly positive correlation (ρ = 0.367; P < .001). Overexpression of PARP-1 correlated with a complex karyotype (P = .030), and this correlation remained significant for coexpression of PARP-1 and Bcl-2 proteins (χ(2) = 7.498; P = .024) as well as after exclusion of pediatric patients (n = 9, P = .042). Overexpression of PARP-1 was not significantly more common in diploid versus aneuploid karyotypes (50% versus 59%, P = .610). The PARP-1 protein showed no correlation with specific chromosomal abnormalities associated with prognosis in B-ALL, as defined by the World Health Organization. In conclusion, high expression of the PARP-1 protein among patients with B-ALL is related to a complex karyotype and Bcl-2 positivity. Although these findings require validation in a larger population, the observations will be valuable in planning therapeutic trials (such as of PARP inhibitors and BH3 mimetics).

Monocytopenia as a diagnostic clue to pediatric B-lymphoblastic leukemia with rare circulating blasts.

B-lymphoblastic leukemia/lymphoma (B-LL) is the most common childhood cancer. Circulating blasts in the peripheral blood may be rare (≤1%) and missed, even when flow cytometric immunophenotyping is performed, leading to a false-negative report. The records from all patients with a new diagnosis of B-LL between January 2009 and December 2011 at our institution were reviewed. Of 130 cases with peripheral blood flow cytometry, 15 had a blast count of ≤1%, with 14 having electronic files for gating monocytes. The percentage of monocytes by flow cytometry and absolute monocyte counts (AMCs) were compared with peripheral blood samples that were negative by flow cytometry, sent due to cytopenia of at least 1 lineage (n = 39). The monocytes from the patients with leukemia averaged 0.8% and were statistically fewer than the negative controls, which averaged 7.1% (P < 0.001). Eleven of the 14 (79%) patients with leukemia had monocytes <1%, compared to only 3 (8%) of the negative controls. The AMCs were also significantly lower (P < 0.001), with 93% of the leukemia group having an AMC <100 cells/µL, compared to only 28% of the negative controls. In patients with cytopenias, percentage of monocytes may be an important diagnostic clue in determining the presence of occult leukemia. If flow cytometry is performed, acquisition of more than the standard 10,000 events is necessary to adequately assess for leukemia. If monocytes are <1% by flow cytometry in the setting of cytopenias, bone marrow examination is recommended, even with negative peripheral blood flow cytometry.

Monocytopenia as a diagnostic clue to pediatric B-lymphoblastic leukemia with rare circulating blasts.

Abstract Background: B-lymphoblastic leukemia/lymphoma (B-LL) is the most common childhood cancer. Occasionally, circulating blasts in the peripheral blood are rare ({less than or equal to}1%) and may be missed, even when flow cytometric immunophenotyping is performed, leading to a false negative report. Methods: The records from all patients with a new diagnosis of B-LL at our institution were reviewed from Jan 2009-Dec 2011. Of 130 cases with peripheral blood flow cytometry, 15 had a blast count of {less than or equal to}1%, with 14 having electronic files for gating monocytes. The percentage of monocytes by flow cytometry and absolute monocyte counts (AMCs) were compared with peripheral blood samples that were negative by flow cytometry, sent due to at least one lineage cytopenia (n=39). Results: The monocytes from the patients with leukemia averaged 0.8%, and were statistically lower than the negative controls, which averaged 7.1% (p<0.001). 11 of the 14 (79%) patients with leukemia had monocytes <1%, compared to only 3 (8%) of the negative controls. The AMCs were also significantly lower (p<0.001), with 93% of the leukemia group having an AMC of <100 cells/µL, compared to only 28% of the negative controls. Conclusions: In patients presenting with cytopenias, assessment of percentage monocytes may be an important diagnostic clue in determining the presence of occult leukemia. If flow cytometry is performed, acquisition of more than the standard 10,000 events is necessary to adequately assess for leukemia. If monocytes are <1% by flow cytometry in the setting of cytopenias, bone marrow examination is recommended, even with negative peripheral blood flow cytometry.

Stability of Leukemia-Associated Immunophenotypes in Precursor B-Lymphoblastic Leukemia/Lymphoma

Essentially all cases of precursor B-lymphoblastic leukemia/lymphoma (B-ALL) demonstrate multiple immunophenotypic aberrancies relative to normal maturing B-cell precursors (hematogones). The stability of these aberrancies has relevance to follow-up minimal residual disease analysis. We compared the immunophenotypes at diagnosis and relapse in 51 childhood and adult B-ALLs with flow cytometry (FC) using broad antibody panels. A total of 446 aberrancies were present at diagnosis (median, 9 per case; range, 2-14). All cases retained multiple aberrancies at relapse (median, 8 per case; range, 2-14). Antibody panels at relapse allowed assessment of 383 (85.9%) of the initial 446 aberrancies. Of these, 299 (78.1%) were persistent and 84 (21.9%) were lost at relapse. Overall, 73% of cases showed a loss of at least 1 aberrancy at relapse. However, new aberrancies were detected in 60% of cases. These findings suggest that FC is suitable for the detection of residual B-ALL, provided that follow-up studies are not too narrowly targeted.