[CD34(+)CD19(+) cells with CD123 overexpression are a novel prognostic marker in Ph chromosome-positive acute
Yuan Kong1, Xiao-Jun Huang2, Le Hao1
1Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
Insights
CD123 expression on CD34(+)CD19(+) cells serves as a novel minimal residual disease (MRD) biomarker in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). Multiparameter flow cytometry (MFC) detection of CD123 overexpression on these cells is an efficient tool for MRD assessment.
Area of Science:
- Hematology
- Immunology
- Oncology
Context:
- Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) is an aggressive hematologic malignancy.
- Accurate monitoring of minimal residual disease (MRD) is crucial for treatment stratification and prognosis in Ph(+)ALL patients.
- Current MRD detection methods, such as RQ-PCR, have limitations and novel biomarkers are needed.
Purpose:
- To investigate CD123 expression characteristics on CD34(+)CD19(+) cells in Ph(+)ALL patients.
- To evaluate the prognostic significance of CD123 expression as a novel MRD biomarker.
- To compare MFC-based detection of CD123(+)CD34(+)CD19(+) cells with RQ-PCR for MRD assessment.
Summary:
- CD123 expression is significantly elevated on CD34(+)CD19(+) cells in both newly diagnosed and relapsed Ph(+)ALL patients compared to normal B-cell progenitors.
- Multiparameter flow cytometry (MFC) detected CD34(+)CD19(+) cells with CD123 overexpression in all Ph(+)ALL patients.
- A strong correlation was observed between MFC and RQ-PCR for MRD detection, with MFC identifying relapse earlier in some cases.
Impact:
- CD123 expression on CD34(+)CD19(+) cells identified by MFC is a promising and efficient biomarker for MRD assessment in Ph(+)ALL.
- This approach can serve as a complementary tool to RQ-PCR, aiding in risk stratification and early detection of relapse.
- The findings contribute to improved management strategies for Ph(+)ALL patients.
Abstract:
This study was aimed to investigate the characteristics of CD123 expression on CD34(+)CD19(+) cells and its prognostic significance as a novel MRD biomarker in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) patients. Consecutive newly diagnosed Ph(+)ALL patients (n = 49) in Peking University Institute of Hematology from January 2010 to April 2012 were prospectively enrolled in this study. At diagnosis and different time points during treatment, CD123 expression on CD34(+)CD19(+) cells was examined by multiparameter flow cytometry(MFC). More than 10 CD34(+)CD19(+) cells with CD123 overexpression in bone marrow samples after complete remission were defined as FCM positive (FCM(+)). The BCR-ABL1[STBZ] transcript was detected by real-time quantitative polymerase chain reaction (RQ-PCR) concurrently. The results showed that mean fluorescence intensity of CD123 on CD34(+)CD19(+) cells in newly diagnosed Ph(+)ALL and relapsed Ph(+)ALL patients was significantly higher than that of normal B-cell progenitors [8.52(3.71-32.35) vs 8.93(4.79-29.74) vs 1.31(0.21-1.75), P < 0.05]. In addition, ratio of the CD34(+)CD19(+) cells with CD123 overexpression in newly diagnosed Ph(+)ALL and relapsed Ph(+)ALL patients were significantly higher than that of normal B-cell progenitors [84.63% (55.07%-99.96%) vs 84.50% (57.68%-99.80%) vs 0.99% (0.45%- 1.83%), P < 0.05]. CD34(+)CD19(+) cells with CD123 overexpression were detected in all newly diagnosed and relapsed Ph(+)ALL patients. A good correlation was found between the MRD results of CD34(+)CD19(+) cells with CD123 overexpression detected by MFC and that detected by RQ-PCR (n = 360 pairs, Spearman r = 0.90, P < 0.0001). Among 13 cases relapsed during follow up, 11 cases of them were detected by FCM(+) at a median time of 60 (30-73) days before the recurrence. It is concluded that as a complementary to RQ-PCR, detection of the CD34(+)CD19(+) cells with CD123 overexpression by MFC promises to be an efficient tool for MRD assessment and risk stratification in human Ph(+)ALL.
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