The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.
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The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line.
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PICALM is involved in clathrin-mediated endocytosis, an essential step in intracellular trafficking of proteins and lipids.
“It has been shown that like BIN1, PICALM is involved in clathrinmediated endocytosis (CME), an essential step in the intracellular trafficking of proteins and lipids such as nutrients, growth factors and neurotransmitters 36-38.”
From Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (2009) · cites this paper as [37]
The Discussion describes clathrin-coated vesicles as important in receptor-mediated endocytosis and vesicle traffic. It proposes that CALM could contribute to endocytotic activity and receptor turnover, but does not establish PICALM's involvement as a demonstrated fact or address trafficking of lipids and the listed cargoes. (LLM, conf=0.85)
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References 52 · Cited by 310
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- S., Taillon-Miller, P., Lichter, P., Evans, G. A., Kersey, J. H., Ward, D. C., Domer, P. H. & Le Beau, M. M. (1990) Proc. Natl. Acad. Sci. USA 87, 9358-9362.
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- Authors
- Dreyling, M. H., Martinez-Climent, J. A., Zheng, M., Mao, J., Rowley, J. D., & Bohlander, S. K.
- Affiliations
- University of Chicago (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-05-14
- Volume
- 93
- Issue
- 10
- Pages
- 4804-4809
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC39360
- OpenAlex
- W2059089115
- Cited by
- 310
- References
- 52
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 6 · 2023: 12 · 2022: 7 · 2021: 9 · 2020: 8 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 20 · 2013: 18 · 2012: 12
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R35CA042557, CA-42557)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- AF10, CALM, gene fusion, acute myeloid leukemia, acute lymphoblastic leukemia, clathrin, phosphoinositide binding, transcription factors, chromosomal translocation
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell Line, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 11, Cloning, Molecular, Humans, Molecular Sequence Data, Monocytes, Nerve Tissue Proteins, Phosphoproteins, Transcription Factors, Translocation, Genetic, Tumor Cells, Cultured, Leukemia, Myeloid, Acute, Sequence Homology, Amino Acid, In Situ Hybridization, Fluorescence, DNA Primers, DNA, Complementary, Adaptor Proteins, Vesicular Transport, Monomeric Clathrin Assembly Proteins, Mice
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