Aberrant DNA methylation of the Src kinase Hck, but not of Lyn, in Philadelphia chromosome negative acute lymphocytic leukemia.
Leukemia
; 21(5): 906-11, 2007 May.
Article
in En
| MEDLINE
| ID: mdl-17344919
ABSTRACT
Hck and Lyn are required in Philadelphia chromosome (Ph) positive acute lymphocytic leukemia (ALL). Here, we present evidence that the promoter CpG island of Hck, but not of Lyn, is aberrantly methylated in leukemia. Hck promoter DNA methylation was detected in 13 out of 23 (56.5%) hematopoietic and eight out of 10 (80%) non-hematopoietic cell lines, but not in normal controls. Treatment with 5-aza-2'-deoxycytidine induced demethylation and restoration of Hck mRNA and protein expression. Hck methylation (> or =15%) was detected in nine out of 44 (20%) patients with Ph negative ALL, and in one out 16 (6%) patients with Ph positive ALL, but not in patients with AML or chronic myelogenous leukemia. In this subset of patients, low levels of Hck methylation (10-15%) were observed in 26-30% of patients. Lyn methylation was observed in three out of 28 (10.7%) cell lines, but only in one out of 71 (1.4%) patients. Patients with Ph negative ALL and Hck methylation had a poorer prognosis. These data indicate that Hck may have tumor suppressor properties in BCR-ABL negative leukemia.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Philadelphia Chromosome
/
Src-Family Kinases
/
DNA Methylation
/
Proto-Oncogene Proteins c-hck
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Limits:
Humans
Language:
En
Journal:
Leukemia
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
Year:
2007
Type:
Article
Affiliation country:
United States