{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:07:45Z","timestamp":1773799665458,"version":"3.50.1"},"reference-count":18,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_almed-2024-0202_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Disease monitoring in acute leukemia management is crucial for risk stratification and chemotherapy response assessment. Minimal residual disease (MRD) testing is the most reliable tool, measuring antigenic expression differences between leukemic cells, hematogones, and mature benign B-cells. Modulation of antigen expression during treatment under chemotherapeutic drugs may complicate MRD analysis and detection. The present study investigates immunophenotypic modulation (IM) during chemotherapy phases in children with acute lymphoblastic leukemia (B-ALL), using a modified BFM protocol, and its potential implications for MRD detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_almed-2024-0202_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study was conducted at the Hematology Department, Indus Hospital and Health Network, Karachi. All MRD positive cases of pediatric B-ALL (1\u00a0month\u00a0\u221216\u00a0years of age) were included, from April 2019- March 2022. MRD was done on bone marrow aspirate using 8-color flow cytometry. The data from 203 patients, who were MRD positive in bone marrow throughout the evaluation period was considered. The IM was assessed by comparative analysis of the changes in mean fluorescence intensity (MFI) of nine highly relevant antigens expressed by the leukemic\u00a0cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_almed-2024-0202_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Statistically significant changes in the MFI levels of antigens were observed in leukemic blasts and mature benign B-cells. All the analyzed samples revealed IM to different extents. Our results confirm the presence of immunophenotypic changes for CD10, CD19, CD34, CD45, TdT, and CD66 during chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_almed-2024-0202_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Measuring the MRD assists in monitoring the disease, however, IM of the different antigens expressed by the leukemic blasts should be considered and cautiously analyzed to prevent erroneous results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/almed-2024-0202","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:57:04Z","timestamp":1746172624000},"page":"358-364","source":"Crossref","is-referenced-by-count":0,"title":["Real-time immunophenotypic shifts in pediatric B lymphoblastic leukemia providing implications for minimal residual disease detection"],"prefix":"10.1515","volume":"6","author":[{"given":"Omer","family":"Javed","sequence":"first","affiliation":[{"name":"Department of Hematology , 586034 Indus Hospital and Health Network , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1650-0694","authenticated-orcid":false,"given":"Neelum","family":"Mansoor","sequence":"additional","affiliation":[{"name":"Department of Cytogenetics and Hematology , Indus Hospital and Health Network , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naeem","family":"Jabbar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology , Indus Hospital and Health Network , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamza","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Hematology , 586034 Indus Hospital and Health Network , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Talha","family":"Israr","sequence":"additional","affiliation":[{"name":"Department of Hematology , 586034 Indus Hospital and Health Network , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidra","family":"Maqsood","sequence":"additional","affiliation":[{"name":"ORIC , Indus Hospital and Health Network , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saba","family":"Jamal","sequence":"additional","affiliation":[{"name":"Department of Hematology , 586034 Indus Hospital and Health Network , Karachi , Pakistan"},{"name":"Clinical Laboratories and Blood Transfusion Services , Indus Hospital and Health Network , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatima","family":"Meraj","sequence":"additional","affiliation":[{"name":"Department of Hematology , 586034 Indus Hospital and Health Network , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"2026031722270831829_j_almed-2024-0202_ref_001","doi-asserted-by":"crossref","unstructured":"Amjad, A, Wali, RM, Anjum, S, Mansoor, R. A single institution\u2019s experience with cytogenetic and MRD outcomes in pediatric acute lymphoblastic leukemia. J\u00a0Coll Physicians Surg Pak 2019;29:549\u201352. https:\/\/doi.org\/10.29271\/jcpsp.2019.06.549.","DOI":"10.29271\/jcpsp.2019.06.549"},{"key":"2026031722270831829_j_almed-2024-0202_ref_002","doi-asserted-by":"crossref","unstructured":"Wood, BL. Principles of minimal residual disease detection for hematopoietic neoplasms by flow cytometry. Cytometry B: Clin Cytometry 2016;90:47\u201353. https:\/\/doi.org\/10.1002\/cyto.b.21239.","DOI":"10.1002\/cyto.b.21239"},{"key":"2026031722270831829_j_almed-2024-0202_ref_003","doi-asserted-by":"crossref","unstructured":"Borowitz, MJ, Devidas, M, Hunger, SP, Bowman, WP, Carroll, AJ, Carroll, WL, et al.. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children\u2019s Oncology Group study. Blood J American Society Hematology 2008;111:5477\u201385. https:\/\/doi.org\/10.1182\/blood-2008-01-132837.","DOI":"10.1182\/blood-2008-01-132837"},{"key":"2026031722270831829_j_almed-2024-0202_ref_004","doi-asserted-by":"crossref","unstructured":"Gaipa, G, Basso, G, Maglia, O, Leoni, V, Faini, A, Cazzaniga, G, et al.. Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection. Leukemia 2005;19:49\u201356. https:\/\/doi.org\/10.1038\/sj.leu.2403559.","DOI":"10.1038\/sj.leu.2403559"},{"key":"2026031722270831829_j_almed-2024-0202_ref_005","doi-asserted-by":"crossref","unstructured":"Borowitz, MJ, Wood, BL, Devidas, M, Loh, ML, Raetz, EA, Salzer, WL, et al.. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children\u2019s Oncology Group study AALL0232. Blood J American Society Hematology 2015;126:964\u201371. https:\/\/doi.org\/10.1182\/blood-2015-03-633685.","DOI":"10.1182\/blood-2015-03-633685"},{"key":"2026031722270831829_j_almed-2024-0202_ref_006","doi-asserted-by":"crossref","unstructured":"Burnusuzov, HA, Spasova, MI, Murdjeva, MA, Stoyanova, AA, Mumdziev, IN, Kaleva, VI, et al.. Immunophenotypic modulation of the blast cells in childhood acute lymphoblastic leukemia minimal residual disease detection. Folia Med 2016;58:28. https:\/\/doi.org\/10.1515\/folmed-2016-0004.","DOI":"10.1515\/folmed-2016-0004"},{"key":"2026031722270831829_j_almed-2024-0202_ref_007","doi-asserted-by":"crossref","unstructured":"Dworzak, MN, Gaipa, G, Schumich, A, Maglia, O, Ratei, R, Veltroni, M, et al.. Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: evidence for a drug-induced regulatory phenomenon. results of the AIEOP\u2010BFM\u2010ALL\u2010FLOW\u2010MRD\u2010Study Group. Cytometry B: Clin Cytom: J Int Soc Anal Cytol 2010;78:147\u201353.","DOI":"10.1002\/cyto.b.20516"},{"key":"2026031722270831829_j_almed-2024-0202_ref_008","doi-asserted-by":"crossref","unstructured":"Meraj, F, Jabbar, N, Nadeem, K, Taimoor, M, Mansoor, N. Minimal residual disease in childhood B Lymphoblastic Leukemia and its correlation with other risk factors. Pakistan J Med Sci 2020;36:S20. https:\/\/doi.org\/10.12669\/pjms.36.icon-suppl.1721.","DOI":"10.12669\/pjms.36.ICON-Suppl.1721"},{"key":"2026031722270831829_j_almed-2024-0202_ref_009","doi-asserted-by":"crossref","unstructured":"Diaz, D, Prieto, A, Barcenilla, H, Monserrat, J, Prieto, P, S\u00e1nchez, M, et al.. Loss of lineage antigens is a common feature of apoptotic lymphocytes. J\u00a0Leukoc Biol 2004;76:609\u201315. https:\/\/doi.org\/10.1189\/jlb.0304171.","DOI":"10.1189\/jlb.0304171"},{"key":"2026031722270831829_j_almed-2024-0202_ref_010","doi-asserted-by":"crossref","unstructured":"Rossi, JG, Bernasconi, AR, Alonso, CN, Rubio, PL, Gallego, MS, Carrara, CA, et al.. Lineage switch in childhood acute leukemia: an unusual event with poor outcome. Am J Hematol 2012;87:890\u20137. https:\/\/doi.org\/10.1002\/ajh.23266.","DOI":"10.1002\/ajh.23266"},{"key":"2026031722270831829_j_almed-2024-0202_ref_011","doi-asserted-by":"crossref","unstructured":"Tembhare, PR, Subramanian, PGPG, Ghogale, S, Chatterjee, G, Patkar, NV, Gupta, A, et al.. A high-sensitivity 10-color flow cytometric minimal residual disease assay in B-lymphoblastic leukemia\/lymphoma can easily achieve the sensitivity of 2-in-106 and is superior to standard minimal residual disease assay: a study of 622 patients. Cytometry B Clin Cytometry 2020;98:57\u201367. https:\/\/doi.org\/10.1002\/cyto.b.21831.","DOI":"10.1002\/cyto.b.21831"},{"key":"2026031722270831829_j_almed-2024-0202_ref_012","doi-asserted-by":"crossref","unstructured":"Dworzak, MN, Schumich, A, Printz, D, P\u00f6tschger, U, Husak, Z, Attarbaschi, A, et al.. CD20\u00a0up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood J American Society Hematology 2008;112:3982\u20138. https:\/\/doi.org\/10.1182\/blood-2008-06-164129.","DOI":"10.1182\/blood-2008-06-164129"},{"key":"2026031722270831829_j_almed-2024-0202_ref_013","doi-asserted-by":"crossref","unstructured":"Gaipa, G, Basso, G, Aliprandi, S, Migliavacca, M, Vallinoto, C, Maglia, O, et al.. Prednisone induces immunophenotypic modulation of CD10 and CD34 in nonapoptotic B-cell precursor acute lymphoblastic leukemia cells. Cytometry B: Clin Cytometry: J Int Soc Anal Cytol 2008;74:150\u20135. https:\/\/doi.org\/10.1002\/cyto.b.20408.","DOI":"10.1002\/cyto.b.20408"},{"key":"2026031722270831829_j_almed-2024-0202_ref_014","doi-asserted-by":"crossref","unstructured":"Thulasi Raman, R, Anurekha, M, Lakshman, V, Balasubramaniam, R, Ramya, U, Revathi, R. Immunophenotypic modulation in pediatric B lymphoblastic leukemia and its implications in MRD detection. Leuk Lymphoma 2020;61:1974\u201380. https:\/\/doi.org\/10.1080\/10428194.2020.1742902.","DOI":"10.1080\/10428194.2020.1742902"},{"key":"2026031722270831829_j_almed-2024-0202_ref_015","unstructured":"Cap, J, Babusikova, O, Kaiserova, E, Jamarik, M. Expression of CD10, CD19 and CD34 markers in bone marrow samples of children with precursor B-cell acute lymphoblastic leukemia in clinical and hematological remission. Neoplasma 1998;45:231\u20136."},{"key":"2026031722270831829_j_almed-2024-0202_ref_016","doi-asserted-by":"crossref","unstructured":"Ismail, M, Zaghloul, A, Abdulateef, N, Morsi, H. Membranous expression of pan CD66, CD66a, CD66b, and CD66c and their clinical impact in acute leukemia: cross sectional longitudinal cohort study in Saudi Arabia. J\u00a0Leuk 2017;5:230\u20139.","DOI":"10.4172\/2329-6917.1000230"},{"key":"2026031722270831829_j_almed-2024-0202_ref_017","doi-asserted-by":"crossref","unstructured":"Chowdhury, S, Bandyopadhyay, S, Mandal, C, Chandra, S, Mandal, C. Flow-cytometric monitoring of disease-associated expression of 9-O-acetylated sialoglycoproteins in combination with known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study. BMC Cancer 2008;8:1\u201316. https:\/\/doi.org\/10.1186\/1471-2407-8-40.","DOI":"10.1186\/1471-2407-8-40"},{"key":"2026031722270831829_j_almed-2024-0202_ref_018","doi-asserted-by":"crossref","unstructured":"Akiyama, M, Yamada, O, Agawa, M, Yuza, Y, Yanagisawa, T, Eto, Y, et al.. Effects of prednisolone on specifically expressed genes in pediatric acute B-lymphoblastic leukemia. J\u00a0Pediatr Hematol Oncol 2008;30:313\u20136. https:\/\/doi.org\/10.1097\/mph.0b013e318161a28f.","DOI":"10.1097\/MPH.0b013e318161a28f"}],"container-title":["Advances in Laboratory Medicine \/ Avances en Medicina de Laboratorio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/almed-2024-0202\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/almed-2024-0202\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:27:15Z","timestamp":1773786435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/almed-2024-0202\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,5]]},"references-count":18,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,5,5]]},"published-print":{"date-parts":[[2025,9,19]]}},"alternative-id":["10.1515\/almed-2024-0202"],"URL":"https:\/\/doi.org\/10.1515\/almed-2024-0202","relation":{},"ISSN":["2628-491X"],"issn-type":[{"value":"2628-491X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,5]]}}}