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HIC1 Hypermethylation Is a Late Event in Hematopoietic Neoplasms¹

The Oncology Center [J-P. J. I., B. A. Z., S. H. K., M. A. B., S. B. B.] and the Department of Medicine [S. B. B.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231

HIC1, a candidate tumor suppressor gene on 17p13.3, is hypermethylated and silenced in a large number of solid tumors. To determine its potential role in leukemias, we studied its methylation status in normal and neoplastic hematopoietic cells. We found HIC1 to be unmethylated in peripheral blood cells, bone marrow cells, and CD34+ cells. HIC1 was rarely methylated in newly diagnosed acute myelogenous leukemias (10%) but was relatively frequently methylated in newly diagnosed non-Hodgkin's lymphoma (25%), acute lymphocytic leukemia (ALL; 53%), and chronic-phase chronic myelogenous leukemia (50%). By contrast, HIC1 was hypermethylated in 100% of recurrent ALL and 100% of blast crisis chronic myelogenous leukemia. In two patients with ALL for whom paired diagnosis/relapse samples were available, HIC1 was unmethylated at diagnosis but was highly methylated at relapse after a chemotherapy-induced complete remission. HIC1 methylation, therefore, seems to be a progression event in hematopoietic neoplasms.

¹ Supported by a Young Investigator Award from The American Society of Clinical Oncology (to J-P. J. I.) as well as NIH Grant 5RO1CA43318. S. H. K. is a scholar of the Leukemia Society of America.

² To whom correspondence should be addressed, at The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231.

³ Current address: Washington University, Pediatric Genetics, Box 8116, I Children's Place, St. Louis, MO 63110.

⁴ Current address: Mayo Clinic, 1301 Guggenheim, 200 First Street SW, Rochester, MN 55905.

Received 2/13/97. Accepted 3/17/97.

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