Expression of CD123 in B-Acute Lymphoblastic Leukemia as a Predictor of BCR/ABL rearrangement and Disease Relapse
Abstract
Introduction: CD123 is the alpha chain of the interleukin 3 receptor (IL-3R) and normally expressed on hematopoietic progenitor cells, monocytes, B lymphocytes and endothelial cells. Leukemic stem cells can be detected using CD123, and its usefulness for measuring residual disease and potential involvement in disease relapse is being evaluated. It also regulates the growth, proliferation, survival, and differentiation of hematopoietic cells, along with immunity and inflammatory response. Materials and Methods: Bone marrow or peripheral blood from 50 B-Acute Lymphoblastic Leukemia (B-ALL) patients were enrolled in the study. CD123 expression was studied by flow cytometry technique and correlated with clinical and hematological parameters as well as BCR-ABL status, MRD status and disease status. Results: CD123 expression was found positive in 38% patients. No significant correlation of CD123 expression with clinical and hematological parameters was observed. A significant higher incidence of CD123 expression was noted in patients with BCR-ABL fusion (70%), relapse patients (67%) and MRD patients (67%). Conclusion: CD123 can be used to predict BCR-ABL status in B-ALL patients and it has potential role to recognize high risk of relapse and helps to scrutinize high risk B-ALL patients who benefited with aggressive chemotherapy. Further, higher expression of CD123 in MRD patients can be used to evaluate minimal residual disease in follow-up B-ALL patients.
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10) Hassanein NM, Alcancia F, Perkinson KR, Buckley PJ, Lagoo AS. Distinct expression patterns of CD123 and CD34 on normal bone marrow B-cell precursors (“hematogones”) and B lymphoblastic leukemia blasts. American journal of clinical pathology. 2009 Oct 1;132(4):573-80.
11) Bras AE, de Haas V, van Stigt A, Jongen‐Lavrencic M, Beverloo HB, Te Marvelde JG, Zwaan CM, van Dongen JJ, Leusen JH, van der Velden VH. CD123 expression levels in 846 acute leukemia patients based on standardized immunophenotyping. Cytometry Part B: Clinical Cytometry. 2019 Mar;96(2):134-42.
12) Li Z, Chu X, Gao L, Ling J, Xiao P, Lu J, Wang Y, He H, Li J, Hu Y, Li J. Highexpression of interleukin-3 receptor alpha chain (CD123) predicts favorable outcome in pediatric B-cell acute lymphoblastic leukemia lacking prognosis-defining genomic aberrations. Frontiers in Oncology. 2021 Mar 16;11:614420.
13) Aref S, El Agdar M, Khaled N, Ibrahim L, El-Ghonemy MS. Clinical Impact of CD25/CD123 Coexpression in Adult B-Cell Acute Lymphoblastic Leukemia Patients. Advances in Hematology. 2020 May 20;2020.
14) Gadhia P, Parek N, Chavda P, Bhatia G, Vaniawala S. Cytogenetic findings of patients with acute lymphoblastic leukemia in west Indian region. International Journal of Advanced Research. 2018;6(2):2320-407.
15) Owaidah TM, Rawas FI, Elkum NB. Expression of CD66c and CD25 in acute lymphoblastic leukemia as a predictor of the presence of BCR/ABL rearrangement. Hematology/Oncology and Stem Cell Therapy. 2008 Jan 1;1(1):34-7
2) Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO classification of tumours of haematopoietic and lymphoid tissues. Swerdlow SH, editor. Lyon: International agency for research on cancer; 2008 Sep 20.
3) Angelova E, Audette C, Kovtun Y, Daver N, Wang SA, Pierce S, Konoplev SN, Khogeer H, Jorgensen JL, Konopleva M, Zweidler-McKay PA. CD123 expression patterns and selective targeting with a CD123-targeted antibody-drug conjugate (IMGN632) in acute lymphoblastic leukemia. Haematologica. 2019 Apr;104(4):749.
4) U. Testa, E. Pelosi, and G. Castelli, “CD123 as a therapeutic target in the treatment of hematological malignancies,” Cancers, vol. 11, no. 9, p. 1358, 2019.
5) Ruella M, Barrett DM, Kenderian SS, Shestova O, Hofmann TJ, Perazzelli J, Klichinsky M, Aikawa V, Nazimuddin F, Kozlowski M, Scholler J. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. The Journal of clinical investigation. 2016 Oct 3;126(10):3814-26.
6) Das N, Gupta R, Gupta SK, Bakhshi S, Malhotra A, Rai S, Singh S, Prajapati VK, Sahoo RK, Gogia A, Sharma A. A real-world perspective of CD123 expression in acute leukemia as promising biomarker to predict treatment outcome in B-ALL and AML. Clinical Lymphoma Myeloma and Leukemia. 2020 Oct 1;20(10):e673-84.
7) Broughton SE, Dhagat U, Hercus TR, Nero TL, Grimbaldeston MA, Bonder CS, Lopez AF, Parker MW. The GM–CSF/IL‐3/IL‐5 cytokine receptor family: from ligand recognition to initiation of signaling. Immunological reviews. 2012 Nov;250(1):277-302.
8) Guthridge MA, Stomski FC, Thomas D, Woodcock JM, Bagley CJ, Berndt MC, Lopez AF. Mechanism of activation of the GM-CSF, IL-3, and IL-5 family of receptors. Stem cells. 1998 Sep;16(5):301-13.
9) Djokic M, Björklund E, Blennow E, Mazur J, Söderhäll S, Porwit A. Overexpression of CD123 correlates with the hyperdiploid genotype in acute lymphoblastic leukemia. haematologica. 2009 Jul;94(7):1016.
10) Hassanein NM, Alcancia F, Perkinson KR, Buckley PJ, Lagoo AS. Distinct expression patterns of CD123 and CD34 on normal bone marrow B-cell precursors (“hematogones”) and B lymphoblastic leukemia blasts. American journal of clinical pathology. 2009 Oct 1;132(4):573-80.
11) Bras AE, de Haas V, van Stigt A, Jongen‐Lavrencic M, Beverloo HB, Te Marvelde JG, Zwaan CM, van Dongen JJ, Leusen JH, van der Velden VH. CD123 expression levels in 846 acute leukemia patients based on standardized immunophenotyping. Cytometry Part B: Clinical Cytometry. 2019 Mar;96(2):134-42.
12) Li Z, Chu X, Gao L, Ling J, Xiao P, Lu J, Wang Y, He H, Li J, Hu Y, Li J. Highexpression of interleukin-3 receptor alpha chain (CD123) predicts favorable outcome in pediatric B-cell acute lymphoblastic leukemia lacking prognosis-defining genomic aberrations. Frontiers in Oncology. 2021 Mar 16;11:614420.
13) Aref S, El Agdar M, Khaled N, Ibrahim L, El-Ghonemy MS. Clinical Impact of CD25/CD123 Coexpression in Adult B-Cell Acute Lymphoblastic Leukemia Patients. Advances in Hematology. 2020 May 20;2020.
14) Gadhia P, Parek N, Chavda P, Bhatia G, Vaniawala S. Cytogenetic findings of patients with acute lymphoblastic leukemia in west Indian region. International Journal of Advanced Research. 2018;6(2):2320-407.
15) Owaidah TM, Rawas FI, Elkum NB. Expression of CD66c and CD25 in acute lymphoblastic leukemia as a predictor of the presence of BCR/ABL rearrangement. Hematology/Oncology and Stem Cell Therapy. 2008 Jan 1;1(1):34-7
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Issue | Vol 16 No 1 (2024) | |
Section | Original Articles | |
DOI | https://doi.org/10.18502/bccr.v16i1.18750 | |
Keywords | ||
B-Acute Lymphoblastic Leukemia Flow cytometry CD123 |
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How to Cite
1.
Raiya B. Expression of CD123 in B-Acute Lymphoblastic Leukemia as a Predictor of BCR/ABL rearrangement and Disease Relapse. Basic Clin Cancer Res. 2025;16(1):50-57.