Upregulation of CD146 in Pediatric B-Cell Acute Lymphocytic Leukemia and Its Implications on Treatment Outcomes.

Asmaa M Zahran,Wael M Y Mohamed,Amal Rayan,Khalid I Elsayh,Omnia El-Badawy,Khalid F Riad,Mona H Abdel-Rahim

doi:10.1155/2020/9736159

Asmaa M Zahran, Wael M Y Mohamed + Show 5 more

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https://doi.org/10.1155/2020/9736159

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Abstract

Background and Aim. We studied through flow cytometry the expression of CD146 on different T cells, and B-cell ALL blasts trying to correlate its expression with different prognostic factors of B-cell ALL and treatment outcomes. Patients and Methods. All pediatric patients with B-cell ALL were subjected to bone marrow examination and cytochemistry, flow cytometric immunophenotyping using monoclonal antibodies utilized for diagnosis of B-ALL including CD34, CD19, CD10, CD22, and intracellular IgM. The diagnosis was based on standard morphologic, cytochemical, and immunophenotypic followed by flow cytometric detection of CD146 expression on blast cells, CD4+, and CD8+ T cells. Results Significant accumulations of CD146+CD4+ cells, CD146+CD8+ cells, CD4+, CD8+, and lymphocytes in patients were compared to controls, the mean percentages of CD146+CD4+ cells, CD146+CD8+ cells, and CD146+ blasts were significantly higher in patients than controls, and in addition, these cells were associated with poor overall survival and disease-free survival. The median OS for patients with complete response was 22 ± 1.633 (95%CI = 18.799‐25.201), while for those without complete response, it was 13 ± 3.928 (95%CI = 5.301‐25.699), with log‐rank = 5.71, P = 0.017. Conclusion CD146 was expressed significantly in children's B-ALL and associated with poor prognostic features including poor response and treatment outcomes and could be a possible poor prognostic factor in pediatric B-cell ALL.

Highlights

Acute lymphoblastic leukemia (ALL) is by far the most common pediatric malignancy, representing one quarter of all children cancers
This study involved pediatric patients with B-cell ALL having a median age of 6.5 years; as known for pediatric tumors, male children are exceedingly affected than female ones, so we had a male to female ratio of 1.4 : 1. Most patients were presented with constitutional symptoms including fever in (16/31) patients, whereby their caregivers pursued medical care, hepatomegaly, LN enlargement, and splenomegaly which were presented in 32.3%, 25.8%, and 22.6% of study patients (Table 1)
Upon doing Cox regression analysis, we found that only CD34+ cells were the most independent factor of Overall survival (OS) (HR = 1:039, P = 0:014), while the HR of CD146+CD4+ cells was 2.326 (95%CI = 0:904‐5:982) and was considered the highest one among different immune cells followed by HR of CD146 blasts (HR = 1:023, 95%CI = 0:955‐1:096) (Table 6, Figure 9), as hazard ratio increased the risk of death from induction therapy increased

Summary

Introduction

Acute lymphoblastic leukemia (ALL) is by far the most common pediatric malignancy, representing one quarter of all children cancers. CD146, known as Mel-CAM, MUC18, MCAM, SEndo-1, and P1H12 antigen [3], is a transmembrane glycoprotein belonging to the immunoglobulin family and functions as a Ca2+-independent adhesion molecule [4] It is expressed in normal tissues including smooth muscles, vascular endothelium, and others to exert cation-independent adhesion through interactions with an unidentified ligand. All pediatric patients with B-cell ALL were subjected to bone marrow examination and cytochemistry, flow cytometric immunophenotyping using monoclonal antibodies utilized for diagnosis of B-ALL including CD34, CD19, CD10, CD22, and intracellular IgM.

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Results

Conclusion