Immunophenotypic Modulation of the Blast Cells in Childhood Acute Lymphoblastic Leukemia Minimal Residual Disease
Hasan A Burnusuzov1, Mariya I Spasova1, Mariana A Murdjeva2
1Department of Pediatrics and Medical Genetics, Medical University of Plovdiv, Plovdiv, Bulgaria
Unlabelled:
Early clearance of leukemic cells during induction therapy of childhood acute lymphoblastic leukemia (ALL) is a basis for treatment optimization. Currently, the most widely used methods for the detection of minute residual malignant cells in the bone marrow and/or peripheral blood, minimal residual disease (MRD), are PCR and flow cytometry (FCM). Immunophenotypic modulation (IM) is a well known factor that can hamper the accurate FCM analysis.
Aim:
To report the IM detected by 8-color FCM during the BFM-type remission induction in 24 consecutive MRD-positive samples of children with B-cell precursor ALL and the possible implications for MRD detection.
Patients And Methods:
Between 2010 and 2012 we prospectively followed up the MRD on days 15 and 33 of induction treatment in bone marrow (BM) samples and on day 8 in peripheral blood (PB). The IM was assessed by comparative analyses of the changes in the mean fluorescence intensity of 7 highly relevant antigens expressed by the leukemic cells and normal B-lymphocytes.
Results:
IM occurred, to different extents, in all analyzed day 15 BM and in most day 33 BM samples. Statistically significant changes in the MFI-levels of four CDs expressed by the leukemic blasts were observed: downmodulation of CD10, CD19 and CD34 and upmodulation of CD20. No changes in the expression of CD38, CD58 and CD45 were noticed.
Conclusions:
Measuring the MRD by standardized 8-color flow cytometry helps improve the monitoring of the disease, leading to better therapeutic results. However, the IM of the different antigens expressed by the leukemic blasts should be taken into consideration and cautiously analyzed.
Insights
Immunophenotypic modulation (IM) can affect minimal residual disease (MRD) detection in childhood acute lymphoblastic leukemia (ALL). Careful analysis of antigen expression changes is crucial for accurate MRD monitoring and optimizing treatment.
Area of Science:
- Pediatric Oncology
- Immunology
- Flow Cytometry
Background:
- Early detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) is key for treatment optimization.
- Flow cytometry (FCM) and PCR are standard methods for MRD detection.
- Immunophenotypic modulation (IM) can interfere with accurate FCM-based MRD assessment.
Purpose of the Study:
- To report IM detected by 8-color FCM during induction therapy in pediatric B-cell precursor ALL.
- To evaluate the implications of IM for MRD detection in these patients.
Main Methods:
- Prospective follow-up of MRD in bone marrow and peripheral blood samples during induction therapy (BFM-type).
- Assessment of IM by comparing mean fluorescence intensity (MFI) of antigens on leukemic cells and normal B-lymphocytes.
- Analysis of 24 consecutive MRD-positive samples from children with B-cell precursor ALL.
Main Results:
- IM was observed to varying degrees in most analyzed samples (day 15 BM, day 33 BM).
- Significant changes in MFI included downmodulation of CD10, CD19, and CD34, and upmodulation of CD20 on leukemic blasts.
- No significant changes were noted for CD38, CD58, and CD45 expression.
Conclusions:
- Standardized 8-color FCM improves MRD monitoring and therapeutic outcomes in ALL.
- Immunophenotypic modulation of leukemic blasts must be considered and cautiously analyzed for accurate MRD assessment.
- Accurate MRD detection is vital for tailoring treatment strategies in pediatric ALL.
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