Related Experiment Video
Updated: Feb 11, 2026
08:31
Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
Published on: October 17, 2025
709
Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia
Michelle L Churchman1, Maoxiang Qian2, Geertruy Te Kronnie3
1Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cancer Cell
|April 24, 2018
Summary
Germline variations in the IKZF1 gene predispose children to acute lymphoblastic leukemia (ALL). These IKZF1 variants impact leukemia cell function and drug response, highlighting their role in familial and sporadic ALL development.
Area of Science:
- Genetics
- Oncology
- Pediatric Hematology
Background:
- Somatic IKZF1 alterations are frequent in high-risk B-progenitor acute lymphoblastic leukemia (ALL), correlating with poor prognosis.
- These alterations induce stem cell-like properties, aberrant cell interactions, and reduced sensitivity to tyrosine kinase inhibitors in leukemia cells.
Purpose of the Study:
- To investigate the role of germline IKZF1 variations in familial and sporadic childhood ALL.
- To determine the functional impact of identified germline IKZF1 variants on leukemia cell behavior and drug responsiveness.
Main Methods:
- Sequencing of the IKZF1 gene in children with familial and sporadic B-ALL.
- Functional assays to assess the impact of germline variants on IKZF1 function and drug sensitivity.
Main Results:
- Identified 28 unique coding germline IKZF1 variants in 45 children with ALL (0.9% of presumed sporadic cases).
- The majority of these variants impaired IKZF1 function and decreased leukemic cell sensitivity to drugs.
Conclusions:
- Germline IKZF1 variation is a significant factor in childhood ALL predisposition.
- These findings underscore the importance of germline genetics in both familial and sporadic ALL pathogenesis, impacting therapeutic strategies.
Related Concept Videos
01:25Genetic Variation
1.4K
Genetic variation is the diversity in DNA sequences found among individuals of the same species. This diversity is crucial for a species' survival because it helps organisms adapt to environmental changes. Genetic variation begins with fertilization, where an egg and sperm cell merge. Each of these cells carries 23 chromosomes, up to 46 in the fertilized egg. Chromosomes are long DNA strands that contain genes, the basic units of heredity.
Genes exist in different versions called alleles,...
Genes exist in different versions called alleles,...
1.4K
01:14What is Variation?
18.6K
Apart from the measures of central tendency, distribution, outliers, and the changing characteristics of data with time, an important characteristic of any data set is its variation or spread. In some data sets, the data values are concentrated closely near the mean; in others, the data values are more widely spread out from the mean.
The range, standard deviation, standard error, and variance are the different measures of variation.
Range: The range is the difference between its maximum and...
The range, standard deviation, standard error, and variance are the different measures of variation.
Range: The range is the difference between its maximum and...
18.6K
02:53Conservative Site-specific Recombination and Phase Variation
6.9K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.9K
01:25What is Population Genetics?
65.0K
A population is composed of members of the same species that simultaneously live and interact in the same area. When individuals in a population breed, they pass down their genes to their offspring. Many of these genes are polymorphic, meaning that they occur in multiple variants. Such variations of a gene are referred to as alleles. The collective set of all the alleles within a population is known as the gene pool.
65.0K
01:19Variation
8.1K
An important characteristic of any set of data is the variation in the data. In some data sets, the data values are concentrated closely near the mean; in other data sets, the data values are more widely spread out from the mean. The most common measure of variation, or spread, is the standard deviation, which is the square root of variance.
When independent and dependent variables are plotted on a scatter plot, the slope of a line is a value that describes the rate of change between the two...
When independent and dependent variables are plotted on a scatter plot, the slope of a line is a value that describes the rate of change between the two...
8.1K
01:18Variation of Atmospheric Pressure
4.2K
Change in atmospheric pressure with height is particularly interesting. The decrease in atmospheric pressure with increasing altitude is due to the decreasing gravitational force per unit area as we move away from the surface of the earth.
Assuming the air temperature is constant at a given altitude and that the ideal gas law of thermodynamics describes the atmosphere to a good approximation, one can find the variation of atmospheric pressure with height.
Let p(y) be the atmospheric pressure at...
Assuming the air temperature is constant at a given altitude and that the ideal gas law of thermodynamics describes the atmosphere to a good approximation, one can find the variation of atmospheric pressure with height.
Let p(y) be the atmospheric pressure at...
4.2K