Publications by authors named "M Torres-Diz"
Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer-related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B-ALL patients, suggesting additional mechanisms of resistance. By mining RNA sequencing datasets of paired diagnostic/relapse pediatric B-ALL samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers of resistance to glucocorticoids, antifolates, and thiopurines.
View Article and Find Full Text PDFRelapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer-related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B- ALL patients, suggesting additional mechanisms of resistance. By mining RNA-seq datasets of paired diagnostic/relapse pediatric B-ALL samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers of resistance to glucocorticoids, anti-folates, and thiopurines.
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- Aberrant splicing of the MS4A1 gene results in multiple mRNA isoforms of CD20, with V1 and V3 being the most significant in B-cell malignancies and immune responses.
- The presence of V3 correlates with higher CD20 protein levels, while V1 is likely translation-deficient due to structural elements that inhibit protein synthesis.
- Studies show that modulating these isoforms can enhance CD20 expression and improve the effectiveness of anti-CD20 therapies, highlighting a potential link between splicing patterns and immunotherapy resistance.
Article Synopsis
- The gene encoding CD20 in human B cells produces multiple mRNA isoforms, particularly V1 and V3, which play different roles in B-cell malignancies and immunotherapy responses.
- Increased CD20 positivity during B-cell activation correlates with the shift from V1 to V3, and only V3 is associated with higher CD20 protein levels in diffuse large B-cell lymphoma.
- Manipulating CD20 isoform expression can enhance the effectiveness of anti-CD20 therapies, revealing that splicing changes may contribute to resistance in immunotherapy, particularly evident in relapsed follicular lymphoma cases.
Elucidating the adaptive mechanisms that prevent host immune response in cancer will help predict efficacy of anti-programmed death-1 (PD1)/L1 therapies. Here, we study the cell-intrinsic response of lung cancer (LC) to interferon-γ (IFNγ), a cytokine that promotes immunoresponse and modulates programmed death-ligand 1 (PD-L1) levels. We report complete refractoriness to IFNγ in a subset of LCs as a result of JAK2 or IFNGR1 inactivation.
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