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Biomedical subjects

G Yoffe

Publications and source records attributed to G Yoffe.

12 recordsLinked to original sources
PubMed1989

The chromosome translocation (11;14)(p13;q11) associated with T-cell acute lymphocytic leukemia: an 11p13 breakpoint cluster region.

The translocation (11;14)(p13;q11) was observed in karyotypes of leukemic cells from a 3-year-old boy with T-cell acute lymphocytic leukemia (T-ALL). Since this translocation is a recurrent marker of T-ALL, we undertook to investigate its mode of formation and role in leukemogenesis. The cytogenetic breakpoint on chromosome 14 occurs in 14q11, the same band wherein lies the T-cell receptor alpha/delta chain gene; and Southern hybridization analysis of peripheral blood and bone marrow DNA uncovered a tumor-specific rearrangement in the D delta-J delta region of this locus. DNA encompassing the rearrangement was isolated by molecular cloning, and further analysis revealed it to be the t(11;14)(p13;q11) junction. Nucleotide sequence determination of the junction indicates that the 14q11 breakpoint occurs immediately adjacent to the D delta 2 gene segment. Hence, the translocation arose as an aberrant rearrangement between the downstream recombination signal of D delta 2 and a pseudo recombination signal adjacent to the chromosome 11 breakpoint. Finally, comparison of the breakpoint in band 11p13 with those of other translocations (11;14)(p13;q11) identified a breakpoint cluster region of approximately 1.2 kilobase-pairs (kb), alterations of which may promote the development of T-ALL.

Base Sequence↗
PubMed1988

Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia-positive chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between chromosomes 9 and 22. The breakpoints on chromosome 22 are clustered within a 5.8-kilobase (kb) DNA fragment known as the breakpoint cluster region (bcr), which encodes part of a functionally active gene. We analyzed the bcr in DNAs from 108 consecutive, unselected Philadelphia chromosome-positive CML patients by Southern blot and determined five restriction enzyme fragments within which breaks occur on chromosome 22. The exact sublocalization was determined in the DNA of 100 patients. It was found to be within the 5.8-kb in 99 patients and outside the bcr in only one. Within the bcr, most of the breakpoints occurred in fragments 1, 2, and 3. Overall, laboratory and clinical features of CML did not correlate with specific breakpoint fragments, but chronic-phase duration was longer in patients with a breakpoint in fragment 2 of the bcr. Large 3' bcr deletions were found in nine patients but did not influence clinical outcome. DNA from one of six patients analyzed both during chronic phase and blastic crisis showed an additional aberrant fragment, which suggested that a second abnormal clone developed in blastic crisis.

Blast Crisis↗
PubMed1987

Clonal nature of Philadelphia chromosome-positive and -negative chronic myelogenous leukemia by DNA hybridization analyses.

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.

Adult↗
PubMed1987

Molecular analysis of interferon-induced suppression of Philadelphia chromosome in patients with chronic myeloid leukemia.

Treatment with recombinant human interferon alpha-A (Roferon-A) is associated with stable suppression of the population of cells that display the Philadelphia (Ph1) chromosome in some patients with chronic myelogenous leukemia (CML) as defined by cytogenetic analysis. Southern blot analyses employing a 3' breakpoint cluster region (bcr) probe (Pr-1) were performed to confirm a complete suppression of the Ph1+ chromosome-positive clone of cells at the DNA level. The complete disappearance of rearranged restriction fragments of the bcr gene, which were a characteristic of the disease prior to Roferon-A therapy, was accompanied by the restoration of normal bone marrow and achievement of durable ongoing complete remission for 9 and 6 months, respectively, in two patients with Philadelphia-positive (Ph1+) CML. Molecular analysis is a valuable probe for monitoring the clinical course of disease in patients with Ph1+ CML.

Adult↗
PubMed1987

Determination of clonality in acute nonlymphocytic leukemia by restriction fragment length polymorphism and methylation analysis.

Determination of cellular clonality in hematological malignancies provides fundamental information that is important in understanding the pathogenesis of these disorders. We present here an extension of one approach to accomplish this that is based on the interpretation of different methylation patterns on active and inactive X chromosomes within the region of the hypoxanthine-guanine phosphoribosyltransferase gene spanned by a restriction fragment length polymorphism. The successful application of the method to determine clonality is described for three female patients with acute nonlymphocytic leukemia.

Acute Disease↗
PubMed1985

Impaired immune function in hemophilia patients treated exclusively with cryoprecipitate: relation to duration of treatment.

Recently, abnormalities of cell-mediated immunity were found in hemophiliac patients receiving factor VIII concentrate therapy. Contradictory results were reported concerning cellular immune functions in hemophiliacs treated only with cryoprecipitate or fresh frozen plasma. Therefore, we evaluated the immunological status of 15 Israeli patients with severe classic hemophilia-A who were treated only with cryoprecipitate and never exposed to factor VIII concentrate whether of commercial source or blood bank prepared. As a group, only mildly depressed cellular immune functions and slight reduction in the helper to suppressor cell ratio were found. However, when patients treated more than 15 years were analyzed separately, a significant reduction in proportion of T cells, T-helper cells, helper to suppressor ratio, and proliferative response to phytohemaglutinin and pokeweed mitogen were observed compared to patients treated for less than 15 years and normal controls. Proportion of T-suppressor cells, Con A-activated suppressor activity, and IgG and IgA levels were significantly elevated in patients treated for more than 15 years. These results may support the view that derangement of immune function in hemophiliacs results from infusion of foreign proteins or an ubiquitous virus rather than contracting AIDS infectious agent.

Acquired Immunodeficiency Syndrome↗