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Germline mutation of the p27/Kip1 gene in childhood acute lymphoblastic leukemia

Leukemia volume 16, pages 956–958 (2002)Cite this article

In the past few years, understanding of the cell cycle has rapidly advanced.1 During cellular proliferation, cyclins and cyclin-dependent kinases (CDKs) play important roles in the cell cycle. Recently, a newly recognized family of proteins which inhibit CDKs have been identified. These cyclin-dependent kinase inhibitors (CDKIs) form two classes: the CDKN2B/INK4B/p15, CDKN2/INK4A/p16 and p18/INK4C genes form one class; the second class includes p21/WAF1, p27/Kip1 and p57. These homologous proteins bind to a variety of CDK–cyclin complexes. By regulating cyclin–CDK complex activity, individual CDKIs are potential tumor suppressors. Therefore, their inactivation might contribute to the development of cancer. Indeed, mutations and deletions of CDKN2B/INK4B/p15 and CDKN2/INK4A/p16 are common in many kinds of human malignancies.2

Transforming growth factor β (TGF-β) may induce cell growth arrest through p27/Kip1 activation. TGF-β often loses its ability to arrest growth of transformed cells; this could potentially occur through a defect in p27/Kip1. Recent studies have shown that reduced or lack of p27 expression is associated with poor prognosis in breast, colorectal, prostate and lung cancers, as well as malignant lymphomas.3 Moreover, point mutations of the p27/Kip1 gene were identified in both breast cancer and adult T cell leukemia/lymphoma (ATL) samples, and homozygous deletions of the p27/Kip1 gene were found in both non-Hodgkin's lymphoma (NHL) and ATL samples.4 These findings suggest that p27 is an important tumor suppressor. However, an inactivating mutation of the p27/Kip1 gene has not been identified in childhood acute lymphoblastic leukemia (ALL). In this report, we describe a biallelic inactivation of the p27/Kip1 gene identified in a case with childhood ALL.

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Acknowledgements

This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan (ST) as well as the Parker Hughes Trust, Lymphoma Foundation of America, The Horn Foundation, and NIH grants (HPK).

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Authors and Affiliations

  1. Department of Internal Medicine, Kochi Medical School, Kochi, Japan

    C Takeuchi, S Takeuchi, T Ikezoe & H Taguchi

  2. Institute of Human Genetics, University of Heidelberg, Heidelburg, Germany

    CR Bartram

  3. Division of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, CA, USA

    HP Koeffler

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Takeuchi, C., Takeuchi, S., Ikezoe, T. et al. Germline mutation of the p27/Kip1 gene in childhood acute lymphoblastic leukemia. Leukemia 16, 956–958 (2002). https://doi.org/10.1038/sj.leu.2402408

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