Aberrant methylation in promoter-associated CpG islands of multiple genes in chronic myelogenous leukemia blast crisis

Uehara,Eisuke; Takeuchi,Seisho; Yang,Yang; Fukumoto,Tetsuya; Matsuhashi,Yoshiko; Tamura,Takahiro; Matsushita,Masahide; Nagai,Masami; Koeffler,H.  Phillip; Tasaka,Taizo

doi:10.3892/ol.2011.419

January 2012 Volume 3 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

January 2012 Volume 3 Issue 1

Full Size Image

Article

Aberrant methylation in promoter-associated CpG islands of multiple genes in chronic myelogenous leukemia blast crisis

Authors:
- Eisuke Uehara
- Seisho Takeuchi
- Yang Yang
- Tetsuya Fukumoto
- Yoshiko Matsuhashi
- Takahiro Tamura
- Masahide Matsushita
- Masami Nagai
- H. Phillip Koeffler
- Taizo Tasaka
View Affiliations / Copyright

Affiliations: First Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan, Department of Medicine, Kochi Medical School, Kochi 783-8505, Japan, Department of Internal Medicine, Kagawa Prefectural Central Hospital, Kagawa, Japan, Department of Internal Medicine, Tokushima Prefectural Central Hospital, Tokushima, Japan, Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA
Pages: 190-192
|
Published online on: September 13, 2011

https://doi.org/10.3892/ol.2011.419
Expand metrics +

Abstract

Chronic myelogenous leukemia (CML) has a typical progressive course with transition from a chronic phase to a terminal blast crisis phase. The mechanisms that lead to disease progression remain to be elucidated. To understand the role of aberrant methylation in the progression of CML, DNA methylation patterns in 16 patients with CML blast crisis were analyzed. Methylation status was analyzed by methylation‑specific PCR (MSP) for 13 genes, including cell cycle regulating genes, DNA repair genes, apoptosis‑related genes, a differentiation-associated gene and a cytokine signaling gene. The frequency of samples with methylation in each of the following genes were: p15, 18%; MGMT, 12%; RARβ, 12%; p16, 6%; DAPK, 6% and FHIT, 6%. In total, four (25%) cases showed methylation of at least one gene. None of the 16 cases showed hypermethylation of the hMLH1 or hMSH2 genes. These results suggest that hypermethylation of cell cycle control genes, but not DNA mismatch repair genes, play a significant role in the progression of CML.

View Figures

View References

1	Shet AS, Jahagirdar BN and Verfaillie CM: Chronic myelogenous leukemia: mechanisms underlying disease progression. Leukemia. 16:1402–1411. 2002. View Article : Google Scholar : PubMed/NCBI
2	Randhawa GS, Cui H, Barletta JA, et al: Loss of imprinting in disease progression in chronic myelogenous leukemia. Blood. 91:3144–3147. 1998.PubMed/NCBI
3	Santini V, Kantarjian HM and Issa JP: Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications. Ann Intern Med. 134:573–86. 2001. View Article : Google Scholar : PubMed/NCBI
4	Asimakopoulos FA, Shteper PJ, Krichevsky S, et al: ABL1 methylation is a distinct molecular event associated with clonal evolution of chronic myeloid leukemia. Blood. 94:2452–2460. 1999.PubMed/NCBI
5	Sacchi S, Kantarjian HM, O'Brien S, et al: Chronic myelogenous leukemia in nonlymphoid blastic phase: analysis of the results of first salvage therapy with three different treatment approaches for 162 patients. Cancer. 86:2632–2641. 1999. View Article : Google Scholar
6	Hofmann WK, Tsukasaki K, Takeuchi N, Takeuchi S and Koeffler HP: Methylation analysis of cell cycle control genes in adult T-cell leukemia/lymphoma. Leuk Lymphoma. 42:1107–1109. 2001. View Article : Google Scholar : PubMed/NCBI
7	Uehara E, Takeuchi S, Tasaka T, et al: Aberrant methylation in promoter-associated CpG islands of multiple genes in therapy-related leukemia. Int J Oncol. 23:693–696. 2003.PubMed/NCBI
8	Nguyen TT, Mohrbacher AF, Tsai YC, et al: Quantitative measure of c-abl and p15 methylation in chronic myelogenous leukemia: biological implications. Blood. 95:2990–2992. 2000.PubMed/NCBI
9	Kusy S, Cividin M, Sorel N, et al: p14ARF, p15INK4b, and p16INK4a methylation status in chronic myelogenous leukemia. Blood. 101:374–375. 2003. View Article : Google Scholar
10	Sheikhha MH, Tobal K and Liu Yin JA: High level of microsatellite instability but not hypermethylation of mismatch repair genes in therapy-related and secondary acute myeloid leukaemia and myelodysplastic syndrome. Br J Haematol. 117:359–365. 2002. View Article : Google Scholar
11	Mori N, Takeuchi S, Tasaka T, et al: Absence of microsatellite instability during the progression of chronic myelocytic leukemia. Leukemia. 11:151–152. 1997. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Aberrant methylation in promoter-associated CpG islands of multiple genes in chronic myelogenous leukemia blast crisis

This article is mentioned in:

Abstract

Figure 1

Figure 2

Related Articles