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T McKeithan

Publications and source records attributed to T McKeithan.

5 recordsLinked to original sources
PubMed1991

Translocation (14;19) in acute biphenotypic leukemia.

Translocation (14;19)(q32;q13.1) is an acquired chromosomal rearrangement that has been associated with chronic lymphocytic leukemia of B-cell phenotype frequently progressing to lymphoma. Molecular analysis suggests that the translocation involves the immunoglobulin heavy chain gene on chromosome 14 and the BCL3 oncogene on chromosome 19. We present the first case of t(14;19) in a patient with acute leukemia. Correlation of detailed cytogenetic and molecular genetic studies, cell surface marker analysis, cytochemistry, and electron microscopy indicated that the leukemic cells were biophenotypic, with characteristics consistent with both myeloid and B-lineage lymphoid differentiation.

Adult↗
PubMed1991

Mouse bcl-3: cDNA structure, mapping and stage-dependent expression in B lymphocytes.

Human B-cell chronic lymphocytic leukemias (CLLs) are malignancies of mature B lymphocytes. A subset of these tumors is associated with a non-random t(14; 19) translocation (Ueshima et al., 1985). Recently a gene (bcl-3) has been identified in the region adjacent to the chromosome 19 breakpoint in this translocation (McKeithan et al., 1987; Ohno et al., 1990). We now report the isolation of cDNA clones of mouse bcl-3. The mouse bcl-3-coding region is 1746 bp long and exhibits 80% identity with human bcl-3 at both the nucleotide and amino acid level. The bcl-3 locus maps to the proximal end of mouse chromosome 7, which is syntenic to human chromosome 19. The bcl-3 probe readily detects particularly abundant amounts of a 1.8 kb mRNA in mouse tumors consisting of follicular center mature B cells and large pre-B cells, but not in small pre-B cells. The bcl-3 pattern of expression is distinctive in the spectrum of B-cell maturation in that bcl-3 transcripts are particularly abundant in B-cell lines immortalized just prior to Ig switch. The bcl-3 pattern of expression also bears close resemblance to that of bcl-2 (Gurfinkel et al., 1987), which is frequently associated with human B follicular lymphomas [t(14; 18)] and some chronic lymphocytic leukemias (Adachi et al., 1989; 1990; Adachi & Tsujimoto, 1989).

Amino Acid Sequence↗
PubMed1989

Location of breakpoints within the major breakpoint cluster region (bcr) in 33 patients with bcr rearrangement-positive chronic myeloid leukemia (CML) with complex or absent Philadelphia chromosomes.

We report the sublocalization of the breakpoint in chromosome 22 in 33 patients with chronic myeloid leukemia (CML) who also had unusual marrow cytogenetics. In 23 patients, the leukemic clones were characterized by Philadelphia (Ph1) chromosomes that arose through complex translocations that involved three or more chromosomes. In the remaining ten patients, there were no detectable Ph1 chromosomes despite molecular evidence for the presence of rearrangements in the major breakpoint cluster region (bcr) of chromosome 22 in all cases. There was no significant difference between the two groups with respect to location of the breakpoints within the bcr. When these two groups of patients were combined, there was a significant excess of breakpoints in one segment of the bcr when compared to the distribution of breakpoints seen in 119 patients with simple 9;22 translocations. The difference in breakpoint distributions did not appear to be entirely attributable to differences between groups in disease duration at the time of study. These data support the notion that the unusual genetic recombinations that give rise to BCR/ABL fusion genes in CML involve specific DNA sequences of BCR (and possibly ABL) and additional, recombinogenic sequences, at least some of which are present in loci known to be nonrandomly involved in complex Ph1 translocations.

Adult↗