ABSTRACT
The pathophysiologic role of the Philadelphia chromosome translocation in chronic myelogenous leukemia (CML) has been known for nearly 20 years. However, the most significant morbidity and mortality in CML are caused by progression to blast crisis, about which comparatively little is known at the molecular level. Genomic imprinting is a chromosomal modification leading to parental-origin-specific gene expression in somatic cells. Recently, we and others have described loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to biallelic rather than monoallelic expression in a wide variety of solid tumors. We have now examined the imprinting status of IGF2 in samples from CML patients in stable phase, accelerated phase, and blast crisis. Five of six stable-phase patients showed normal imprinting, but LOI was found in all six cases of advanced disease (three accelerated phase, three blast crisis), which was statistically highly significant (P < .01). Thus, LOI represents a novel type of genetic alteration in CML that appears to be specifically associated with disease progression.
Subject(s)
DNA, Neoplasm/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Blast Crisis , Chronic Disease , DNA Methylation , Gene Expression Regulation, Neoplastic , Genomic Imprinting , Humans , Insulin-Like Growth Factor II/genetics , Prognosis , RNA, Neoplasm/geneticsABSTRACT
Because of the abundance of the classical form of Kaposi sarcoma (CKS) among Jews and people of Mediterranean origin, studies have been conducted to find an association between CKS and HLA antigens. No conclusive results have been drawn, although in a number of these investigations an increased incidence of HLA-DR5 was reported. In our study 49 CKS patients of Jewish origin were serologically analyzed for HLA class I and class II antigens. We found no significant deviation in serologically defined HLA antigens frequencies between patients and 99 ethnically matched controls. However, a nonsignificant decrease in the frequencies of HLA-DR4, HLA-DR12, and the combination of DR4/DR11 was observed. Then we determined in these patients HLA-DRB1, HLA-DQA1, and DQB1 allelic polymorphism by oligotyping on PCR-amplified DNA. In this molecular analysis the only notable finding was a decreased frequency of the combination HLA-DQA1*0301/DQB1*0301, which appeared in one (2%) patient compared to 13 (13%) of the controls. However, the decrease was not statistically significant. On the basis of both serological and molecular analysis done on a relatively large group of CKS patients, we conclude that there is no significant linkage between HLA antigens and CKS in Jewish population.
