{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:18:01Z","timestamp":1787818681518,"version":"build-2784847793"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cell Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the malignant burgeoning of abnormal B-cell lymphoblasts. In recent years, the use of chimeric antigen receptor T-cell (CAR-T) therapy which targets CD19 antigen present on the surface of B-cells, has gained significant attention as a treatment option against aggressive and refractory forms of B-ALL. However, the loss of CD19 antigen on B-cell surface due to aberrant splicing under therapy pressure has been suggested as one of the main factors for the emerging CAR-T therapy resistance. The primary aim of this study was to elucidate the presence and characteristics of aberrant CD19 splicing patterns in pediatric B-ALL patients at the time of initial diagnosis stage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Herein, using RT-PCR based splice assays we have examined CD19 splicing patterns in 43 primary pediatric B-ALL patient samples spread across various subtypes, and investigated underlying mechanisms harboring aberrant splicing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observe that CD19 isoform lacking exon 5-6 is present in ~ 55% of pediatric patients at the initial diagnosis stage itself. Our in-silico analysis identified splicing regulator MBNL1 as a potential modulator of CD19 exon 5-6 splicing. Subsequent qRT-PCR analysis in patient samples revealed that MBNL1 is overexpressed in patient samples exhibiting exon 5-6 skipping. Furthermore, our functional studies demonstrate that loss of MBNL1 in B-ALL cell line induces exon 5-6 skipping, thereby confirming its mechanistic role in CD19 splicing regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, we for the first time report the existence of aberrantly spliced CD19 isoform lacking exon 5-6 in primary pediatric patients at the diagnosis stage. Our results suggest that this MBNL1 dysregulation contributes to this splicing event, potentially predisposing patients to resistance against CD19-directed immunotherapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40348-025-00207-y","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T09:05:38Z","timestamp":1763370338000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Widespread prevalence of CD19 exon 5\u20136 skipping in primary pediatric B-Cell acute lymphoblastic leukemia patients"],"prefix":"10.1186","volume":"12","author":[{"given":"Devesh","family":"Srivastava","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishant","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Misra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"207_CR1","doi-asserted-by":"publisher","first-page":"448","DOI":"10.3892\/ol.2020.11583","volume":"20","author":"FL Huang","year":"2020","unstructured":"Huang FL, Liao EC, Li CL, Yen CY, Yu SJ (2020) Pathogenesis of pediatric B-cell acute lymphoblastic leukemia: molecular pathways and disease treatments (review). 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