| Title: |
Immunophenotypic shift in the B‐cell precursors from regenerating bone marrow samples: A critical consideration for measurable residual disease assessment in B‐lymphoblastic leukemia |
| Authors: |
Chatterjee, Gaurav; Sriram, Harshini; Ghogale, Sitaram; Deshpande, Nilesh; Khanka, Twinkle; Panda, Devasis; Pradhan, Shiv Narayan; Girase, Karishma; Narula, Gaurav; Dhamane, Chetan; Malik, Nirmlya Roy; Banavali, Shripad; Patkar, Nikhil V.; Gujral, Sumeet; Subramanian, Papagudi G.; Tembhare, Prashant R. |
| Source: |
Cytometry Part B: Clinical Cytometry ; volume 100, issue 4, page 434-445 ; ISSN 1552-4949 1552-4957 |
| Publisher Information: |
Wiley |
| Publication Year: |
2020 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Accurate knowledge of expression patterns/levels of commonly used MRD markers in regenerative normal‐B‐cell‐precursors (BCP) is highly desirable to distinguish leukemic‐blasts from regenerative‐BCP for multicolor flow cytometry (MFC)‐based measurable residual disease (MRD) assessment in B‐lymphoblastic leukemia (B‐ALL). However, the data highlighting therapy‐related immunophenotypic‐shift in regenerative‐BCPs is scarce and limited to small cohort. Herein, we report the in‐depth evaluation of immunophenotypic shift in regenerative‐BCPs from a large cohort of BALL‐MRD samples. Ten‐color MFC‐MRD analysis was performed in pediatric‐BALL at the end‐of‐induction (EOI), end‐of‐consolidation (EOC), and subsequent‐follow‐up (SFU) time‐points. We studied normalized‐mean fluorescent intensity (nMFI) and coefficient‐of‐variation of immunofluorescence (CVIF) of CD10, CD19, CD20, CD34, CD38, and CD45 expression in regenerative‐BCP (early, BCP1 and late, BCP2) from 200 BALL‐MRD samples, and compared them with BCP from 15 regenerating control (RC) TALL‐MRD samples and 20 treatment‐naïve bone‐marrow control (TNSC) samples. Regenerative‐BCP1 showed downregulation in CD10 and CD34 expression with increased CVIF and reduced nMFI ( p < 0.001), upregulation of CD20 with increased nMFI ( p = 0.014) and heterogeneous CD45 expression with increased CVIF ( p < 0.001). Immunophenotypic shift was less pronounced in the BCP2 compared to BCP1 compartment with increased CVIF in all but CD45 ( p < 0.05) and reduced nMFI only in CD45 expression ( p = 0.005). Downregulation of CD10/CD34 and upregulation of CD20 was higher at EOI than EOC and SFU time‐points ( p < 0.001). Regenerative‐BCPs are characterized by the significant immunophenotypic shift in commonly used B‐ALL‐MRD markers, especially CD10 and CD34 expression, as compared to treatment‐naïve BCPs. Therefore, the templates/database for BMRD analysis must be developed using regenerative‐BCP. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/cyto.b.21951 |
| Availability: |
https://doi.org/10.1002/cyto.b.21951; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcyto.b.21951; https://onlinelibrary.wiley.com/doi/pdf/10.1002/cyto.b.21951; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cyto.b.21951 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.CB258ECB |
| Database: |
BASE |