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JAGN1 (Jagunal-homolog1) is a ER-resident transmembrane protein which is part of the early secretory pathway and granulocyte colony-stimulating factor receptor mediated signaling. Autosomal recessively inherited variants in the JAGN1 gene lead to congenital neutropenia, early-onset bacterial infections, aphthosis and skin abscesses due to aberrant differentiation and maturation of neutrophils. In addition, bone metabolism disorders and a syndromic phenotype, including facial features, short stature and neurodevelopmental delay, have been reported in affected patients.
View Article and Find Full Text PDFAsciminib resistance of a new BCR::ABL1 p.I293_K294insSSLRD mutant detected in a Ph + ALL patient.
Ann Hematol
January 2025
Univ. Bordeaux, INSERM, BRIC, U1312, Bordeaux, France.
Chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia patients largely benefit from an expanding tyrosine kinase inhibitors (TKIs) toolbox that has improved the outcome of both diseases. However, TKI success is continuously challenged by mutation-driven acquired resistance and therefore, close monitoring of clonal genetic diversity is necessary to ensure proper clinical management and adequate response to treatment. Here, we report the case of a ponatinib-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patient harboring a BCR::ABL1 p.
View Article and Find Full Text PDFEZH2 modulates mRNA splicing and exerts part of its oncogenic function through repression of splicing factors in CML.
Leukemia
January 2025
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
The polycomb protein EZH2 is up-regulated in Chronic Myeloid Leukaemia (CML) and associated with transcriptional reprogramming. Here we tested whether EZH2 might also act as a modulator of the mRNA splicing landscape to elicit its oncogenic function in CML. We treated CML cell lines with EZH2 inhibitors and detected differential splicing of several hundreds of events, potentially caused by the transcriptional regulation of splicing factors.
View Article and Find Full Text PDFPaeoniflorin sensitizes imatinib mesylate-resistant chronic myeloid leukemia cells via the inhibition of Cyr61 production.
Anticancer Drugs
January 2025
Department of Laboratory Medicine, Fujian Medical University Union Hospital, Fuzhou, China.
Imatinib mesylate (IM) is a first-line therapy for chronic myeloid leukemia (CML) and exhibits good therapeutic effects, but not in all patients with CML owing to drug resistance. Our previous study showed that Cyr61 plays a key role in IM resistance in CML cells. Paeoniflorin (PF) is a bioactive compound isolated from the traditional Chinese medicine Paeonia lactiflora Pall that displays anticancer activity.
View Article and Find Full Text PDFTargeting the CD74 signaling axis suppresses inflammation and rescues defective hematopoiesis in -familial platelet disorder.
Sci Transl Med
January 2025
Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Familial platelet disorder (FPD) is associated with germline mutations, establishing a preleukemic state and increasing the risk of developing leukemia. Currently, there are no intervention strategies to prevent leukemia progression. Single-cell RNA sequencing ( = 10) combined with functional analysis of samples from patients with -FPD ( > 75) revealed that FPD hematopoietic stem and progenitor cells (HSPCs) displayed increased myeloid differentiation and suppressed megakaryopoiesis because of increased activation of prosurvival and inflammatory pathways.
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