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
  • Calcium
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics
  • Child
  • Humans
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*/pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma*/genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma*/pathology
  • Zebrafish/genetics
PubMed
38117861 Full text @ PLoS Genet.
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.
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
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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