Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence for the clonal nature of chronic myelogenous leukemia (CML) has been obtained primarily from studies of black females expressing polymorphic glucose-6-phosphate dehydrogenase (G6PD) isoenzymes where, instead of the heterozygous pattern normally found as a result of random X chromosome inactivation, exclusive expression of only one G6PD allele has been demonstrated in leukemic cell populations. We report here the use of two other molecular approaches to examine clonality of peripheral blood cells in patients with CML. The first of these is based on the analysis of consistent differential methylation patterns associated with active and inactive X chromosomes within the region spanned by a BamHI restriction fragment length polymorphism (RFLP) at the hypoxanthine phosphoribosyltransferase (HPRT) locus. By this method, three heterozygous females gave results consistent with monoclonal origin of the disease, including one patient lacking the Philadelphia chromosome (Ph1) normally associated with CML. In the other two patients, both of whom had Ph1-positive CML, clonality was confirmed by the demonstration of simple gene rearrangements by Southern hybridization with a breakpoint cluster region (bcr) probe from chromosome 22.
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PMID:Clonal nature of Philadelphia chromosome-positive and -negative chronic myelogenous leukemia by DNA hybridization analyses. 244 Jul 9

Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) patients consistently show a rearrangement in a 5.8-kilobase length of chromosome 22, referred to as the breakpoint cluster region (bcr). In Ph1-positive acute lymphoblastic leukemia (ALL), the breakpoint in chromosome 22 is more heterogeneous and, in some instances, does not occur within this region. In such cases the cell of origin of the neoplastic clone and the relationship of the disease to CML has remained obscure. We have analyzed the bcr rearrangement in the malignant cells from three patients who presented with Ph1-positive ALL and who in cytogenetic studies had shown evidence of variable involvement of myeloid cells in the Ph1-positive clone. Rearrangements in bcr typical of most cases of CML were detected in purified granulocyte preparations from two of the ALL patients (nos. 1 and 2) and in the blasts from patient 3 at the time of her terminal relapse. In the same analysis the simultaneously obtained granulocytes from patient 3, however, did not show any evidence of bcr rearrangement. Patient 3 was also heterozygous for the BamHI polymorphism in the X-linked hypoxanthine phosphoribosyltransferase (HPRT) gene, thus permitting a different method of clonal analysis based on methylation differences in active and inactive alleles. When DNA from her granulocytes that had shown no bcr rearrangement was hybridized to an HPRT probe, a pattern typical of a polyclonal population was seen. A similar pattern was exhibited by her marrow fibroblasts. In marked contrast, her simultaneously isolated blasts showed an unambiguous monoclonal pattern. These findings demonstrate the origin of the disease in the first two patients in a cell with myelopoietic as well as lymphopoietic potential and confirm the restricted lymphoid cell origin of the neoplastic clone in the third Ph1-positive ALL patient. Furthermore, they indicate that different target cells for transformation within the hematopoietic system may be affected by very similar bcr rearrangements.
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PMID:Molecular analysis of clonality and bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia. 289 31