PUBLICATION

Constitutively active CaMKII Drives B lineage acute lymphoblastic leukemia/lymphoma in tp53 mutant zebrafish

Authors
Rothschild, S.C., Lai, G., Tombes, R.M., Clements, W.K.
ID
ZDB-PUB-231221-9
Date
2023
Source
PLoS Genetics   19: e1011102e1011102 (Journal)
Registered Authors
Clements, Wilson, Rothschild, Sarah Chase, Tombes, Robert M.
Keywords
none
MeSH Terms
  • Animals
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/pathology
  • Calcium
  • Zebrafish/genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma*/genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma*/pathology
  • Child
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics
  • Humans
(all 10)
PubMed
38117861 Full text @ PLoS Genet.
Abstract
Acute lymphoblastic leukemia/lymphoma (ALL) is the most common pediatric cancer and is a malignancy of T or B lineage lymphoblasts. Dysregulation of intracellular Ca2+ levels has been observed in patients with ALL, leading to improper activation of downstream signaling. Here we describe a new zebrafish model of B ALL, generated by expressing human constitutively active CaMKII (CA-CaMKII) in tp53 mutant lymphocytes. In this model, B cell hyperplasia in the kidney marrow and spleen progresses to overt leukemia/lymphoma, with only 29% of zebrafish surviving the first year of life. Leukemic fish have reduced productive genomic VDJ recombination in addition to reduced expression and improper splicing of ikaros1, a gene often deleted or mutated in patients with B ALL. Inhibiting CaMKII in human pre-B ALL cells induced cell death, further supporting a role for CaMKII in leukemogenesis. This research provides novel insight into the role of Ca2+-directed signaling in lymphoid malignancy and will be useful in understanding disease development and progression.
Genes / Markers
Figures
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
sj9TgTransgenic Insertion
    zdf1
      		Point Mutation
      zdf8TgTransgenic Insertion
        zf411TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          No data available
          Fish
          No data available
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          DsRedEFGDsRed
          EGFPEFGEGFP
          GFPEFGGFP
          1 - 3 of 3
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          Mapping
          No data available
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          Citation
          Rothschild, S.C., Lai, G., Tombes, R.M., Clements, W.K. (2023) Constitutively active CaMKII Drives B lineage acute lymphoblastic leukemia/lymphoma in tp53 mutant zebrafish. PLoS Genetics. 19:e1011102e1011102.