Related Experiment Video
Updated: May 16, 2026
08:16
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Recurrent SETBP1 mutations in atypical chronic myeloid leukemia
Rocco Piazza1, Simona Valletta, Nils Winkelmann
1Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
Nature Genetics
|December 11, 2012
Summary
Mutations in the SETBP1 gene were identified in patients with atypical chronic myeloid leukemia (aCML). This discovery reveals SETBP1 as a new oncogene contributing to aCML development and progression.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Atypical chronic myeloid leukemia (aCML) presents similarly to chronic myeloid leukemia (CML) but lacks the characteristic BCR-ABL1 fusion.
- The genetic underpinnings of aCML remain incompletely understood, necessitating further investigation into its molecular drivers.
Purpose of the Study:
- To identify novel somatic mutations in aCML.
- To investigate the role of SETBP1 mutations in the pathogenesis of aCML and related hematological malignancies.
Main Methods:
- Exome sequencing was performed on eight aCML samples.
- Targeted resequencing was conducted on a larger cohort of aCML, diverse hematological malignancies, and cancer cell lines.
- Functional studies assessed the impact of SETBP1 mutations on protein stability, cellular activity, and proliferation.
Main Results:
- Somatic SETBP1 mutations, predominantly p.Gly870Ser, were identified in 17 out of 70 aCML cases (24.3%).
- These mutations, often identical to those in Schinzel-Giedion syndrome, were associated with higher white blood cell counts and poorer prognosis.
- The p.Gly870Ser alteration disrupted ubiquitination, leading to increased SETBP1 and SET protein levels, reduced PP2A activity, and enhanced cell proliferation.
Conclusions:
- Mutated SETBP1 acts as a newly discovered oncogene in aCML and related diseases.
- SETBP1 mutations represent a significant finding in the molecular landscape of aCML.
- Understanding SETBP1's role offers potential therapeutic targets for aCML treatment.
Related Concept Videos
03:18Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...