FNBP1 in Chronic Myeloid Leukemia: Spatial Association with BCR-ABL and Potential Implications for Targeted Therapy

Authors

  • S. Antonenko Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • D. Gurianov Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • I. Kravchuk Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • M. Tesliuk Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • G. Telegeev Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, Kyiv, Ukraine

DOI:

https://doi.org/10.15407/exp-oncology.2026.01.040

Keywords:

chronic myeloid leukemia, BCR-ABL, fNBP1, tyrosine kinase, BCR-ABL/fNBP1 colocalization

Abstract

Background. Chronic myeloid leukemia (CML) develops as a result of the appearance of the oncoprotein BCR-ABL, which, due to its tyrosine kinase activity, leads to abnormal cellular signal transduction and blast transformation. fNBP1 is a protein involved in cytoskeletal remodeling, endocytosis, phagocytosis, and cell migration, but its functional role in the development of CML is unclear. Aim. to investigate the spatial relationship between fNBP1 and the BCR-ABL oncoprotein in CML cells and to assess the potential involvement of fNBP1 in BCR-ABL-related signaling networks. Materials and Methods. The subcellular localization of fNBP1 and BCR-ABL was studied using immunofluorescence staining followed by confocal microscopy in K562 cells. The obtained images were processed and analyzed using fiji software. The bioinformatic analysis of the fNBP1 expression in different cancer types was performed using the GEPIA platform. Results. The bioinformatic analysis revealed a heterogeneous regulation of the fNBP1 expression in vari- ous malignancies, with the largest increase observed in leukemia. A cytoplasmic punctate distribution of fNBP1 was shown in K562 cells. Partial colocalization between fNBP1 and BCR-ABL was found predominantly in the peripheral cytoplasmic regions. Conclusions. The observed common spatial distribution of fNBP1 and BCR-ABL enhances the understanding of this protein complex’s formation, suggesting a potential role for fNBP1 in CML development.

References

Flis S, Chojnacki T. Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities. Drug Des Devel Ther. 2019;13:825-843. https://doi.org/10.2147/DDDT.S191303

Zhang H, Li S. Molecular mechanisms for survival regulation of chronic myeloid leukemia stem cells. Protein Cell. 2013;4(3):186-196. https://doi.org/10.1007/s13238-013-2115-0

Kang J, Liu F, Xu Z, et al. The Philadelphia chromosome in leukemogenesis. Chin J Cancer. 2016;35(1):48. https://doi.org/10.1186/s40880-016-0108-0

Bansal M, Verma M. Potential therapeutic targets in chronic myeloid leukemia. Med Oncol. 2025;42:344. https://doi.org/10.1007/s12032-025-02895-y

Antonenko S, Gurianov D, Telegeev G. Colocalization of USP1 and PH domain of Bcr-Abl oncoprotein in terms of chronic myeloid leukemia cell rearrangements. Cytol Genet. 2016;50:11-15. https://doi.org/10.3103/S0095452716050029

Gurianov D, Antonenko S, Telegeev G. Colocalization of cortactin and PH domain of BCR in HEK293T cells and its potential role in cell signaling. Biopolym Cell. 2016;32(1):26-33. https://doi.org/10.7124/bc.000909

Hamad M. Contribution of BCR-ABL molecular variants and leukemic stem cells in response and resistance to tyrosine kinase inhibitors: a review. F1000Res. 2021;10:1288. https://doi.org/10.12688/f1000research.74570.1

Peiris N, Li F, Donoghue J. BCR: a promiscuous fusion partner in hematopoietic disorders. Oncotarget. 2019;10(28):2738-2754. https://doi.org/10.18632/oncotarget.26837

Antonenko S, Kravchuk I, Telegeev G. Interaction of Bcr-Abl oncoprotein with the Glg1 protein in K562 cells: its role in the pathogenesis of chronic myeloid leukemia. Cytol Genet. 2020;54(1):48-54. https://doi.org/10.3103/S0095452720010028

Antonenko S, Telegeev G. Inhibition of USP1, a new partner of Bcr-Abl, results in decrease of Bcr-Abl level in K562 cells. Exp Oncol. 2020;42:109-114. https://doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-2.14533

Fuchs U, Rehkamp G, Haas OA, et al. The human formin-binding protein 17 (FBP17) interacts with sorting nexin SNX2 and is an MLL-fusion partner in acute myelogenous leukemia. Proc Natl Acad Sci U S A. 2001;98(15):8756-8761. https://doi.org/10.1073/pnas.121433898

Suman P, Mishra S, Chander H. High formin binding protein 17 (FBP17) expression indicates poor differentiation and invasiveness of ductal carcinomas. Sci Rep. 2020;10(1):11543. https://doi.org/10.1038/s41598-020-68454-9

Yamamoto H, Sutoh M, Hatakeyama S, et al. Requirement for FBP17 in invadopodia formation by invasive bladder tumor cells. J Urol. 2011;185(5):1930-1938. https://doi.org/10.1016/j.juro.2010.12.027

Kamioka Y, Fukuhara S, Sawa H, et al. A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis. J Biol Chem. 2004;279(38):40091-40099. https://doi.org/10.1074/jbc.M404899200

English LA, Taylor RJ, Palmos J, et al. F-BAR proteins CIP4 and FBP17 function in cortical neuron radial migration and process outgrowth. J Neurosci. 2025;45(34):e1952242025. https://doi.org/10.1523/JNEUROSCI.1952-24.2025

Aspenström P. Formin-binding proteins: modulators of formin-dependent actin polymerization. Biochim Biophys Acta. 2010;1803:174-182. https://doi.org/10.1016/j.bbamcr.2009.06.002

Yoon BK, Hwang N, Chun KH, et al. Sp1-induced FNBP1 drives rigorous 3D cell motility in EMT-type gastric cancer cells. Int J Mol Sci. 2021;22(13):6784. https://doi.org/10.3390/ijms22136784

Antonenko SV, Gurianov DS, Kravchuk IV, et al. Role of BCR and FNBP1 proteins in phagocytosis as a model of membrane rearrangements with chronic myelogenous leukemia. Cytol Genet. 2023;57:291-297. https://doi.org/10.3103/S0095452723040023

Miroshnychenko D, Dubrovska A, Maliuta S, et al. Novel role of pleckstrin homology domain of the Bcr-Abl protein: analysis of protein–protein and protein–lipid interactions. Exp Cell Res. 2010;316(4):530-542. https://doi.org/10.1016/j.yexcr.2009.11.014

Bolte S, Cordelières FP. A guided tour into subcellular colocalization analysis in light microscopy. J Microsc. 2006;224(Pt 3):213-232. https://doi.org/10.1111/j.1365-2818.2006.01706.x

Adler J, Parmryd I. Colocalization analysis in fluorescence microscopy. Methods Mol Biol. 2013;931:97-109. https://doi.org/10.1007/978-1-62703-056-4_5

Aaron JS, Taylor AB, Chew TL. Image co-localization—co-occurrence versus correlation. J Cell Sci. 2018;131(3):jcs211847. https://doi.org/10.1242/jcs.211847

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Published

14.06.2026

How to Cite

Antonenko, S., Gurianov, D., Kravchuk, I., Tesliuk, M., & Telegeev, G. (2026). FNBP1 in Chronic Myeloid Leukemia: Spatial Association with BCR-ABL and Potential Implications for Targeted Therapy. Experimental Oncology, 48(1), 40–45. https://doi.org/10.15407/exp-oncology.2026.01.040

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Short communications