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Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia
- Source :
- Nature immunology, Swaminathan, S; Klemm, L; Park, E; Papaemmanuil, E; Ford, A; Kweon, SM; et al.(2015). Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nature Immunology, 16(7), 766-774. doi: 10.1038/ni.3160. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/9xc5z50t
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- © 2015 Nature America, Inc. All rights reserved. Childhood acute lymphoblastic leukemia (ALL) can often be traced to a pre-leukemic clone carrying a prenatal genetic lesion. Postnatally acquired mutations then drive clonal evolution toward overt leukemia. The enzymes RAG1-RAG2 and AID, which diversify immunoglobulin-encoding genes, are strictly segregated in developing cells during B lymphopoiesis and peripheral mature B cells, respectively. Here we identified small pre-BII cells as a natural subset with increased genetic vulnerability owing to concurrent activation of these enzymes. Consistent with epidemiological findings on childhood ALL etiology, susceptibility to genetic lesions during B lymphopoiesis at the transition from the large pre-BII cell stage to the small pre-BII cell stage was exacerbated by abnormal cytokine signaling and repetitive inflammatory stimuli. We demonstrated that AID and RAG1-RAG2 drove leukemic clonal evolution with repeated exposure to inflammatory stimuli, paralleling chronic infections in childhood.
- Subjects :
- Male
Adolescent
medicine.medical_treatment
Immunoblotting
Immunology
Mice, Transgenic
Mice, SCID
Biology
Somatic evolution in cancer
Article
Clonal Evolution
Lesion
Mice, Inbred NOD
Cytidine Deaminase
Precursor cell
Tumor Cells, Cultured
medicine
Animals
Humans
Immunology and Allergy
Child
Gene
Childhood Acute Lymphoblastic Leukemia
Homeodomain Proteins
Mice, Knockout
B-Lymphocytes
Reverse Transcriptase Polymerase Chain Reaction
Precursor Cells, B-Lymphoid
Infant
hemic and immune systems
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Flow Cytometry
medicine.disease
3. Good health
DNA-Binding Proteins
Leukemia
Cytokine
Microscopy, Fluorescence
Child, Preschool
Female
medicine.symptom
Clone (B-cell biology)
Antibody Diversity
Subjects
Details
- ISSN :
- 15292916 and 15292908
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Nature Immunology
- Accession number :
- edsair.doi.dedup.....4ee674d3a1317bf095cc35f2b2588e7c