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Biomedical subjects

C Willman

Publications and source records attributed to C Willman.

7 recordsLinked to original sources

Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia.

The t(5;14)(q31;q32) translocation from B-lineage acute lymphocytic leukemia with eosinophilia has been cloned from two leukemia samples. In both cases, this translocation joined the IgH gene and the interleukin-3 (IL-3) gene. In one patient, excess IL-3 mRNA was produced by the leukemic cells. In the second patient, serum IL-3 levels were measured and shown to correlate with disease activity. There was no evidence of excess granulocyte/macrophage colony stimulating factor (GM-CSF) or IL-5 expression. Our data support the formulation that this subtype of leukemia may arise in part because of a chromosome translocation that activates the IL-3 gene, resulting in autocrine and paracrine growth effects.

Base Sequence

Cloning and characterization of the t(15;17) translocation breakpoint region in acute promyelocytic leukemia.

A reciprocal chromosomal translocation, t(15;17)(q22;q11.2-12), is characteristic of acute promyelocytic leukemia (APL) of French-American-British (FAB) subtype M3, and is not associated with any other human malignancy. The non-random pattern of the APL translocations suggests that specific genes on chromosomes 15 and 17 are somehow altered or deregulated as a consequence of the rearrangement. Translocation breakpoints in APL patients provide physical landmarks that suggest an approach to isolating the APL gene(s). Genetic and physical maps constructed for the APL breakpoint region on chromosome 17 have indicated that two fully-linked DNA markers, defining loci for THRA1 and D17S80, map to opposite sides of an APL breakpoint yet reside on a common 350-kb Clal fragment. Cosmid-walking experiments to clone this APL breakpoint have revealed a 38-kilobase deletion on chromosome 17. Studies in additional APL patients have shown that the breakpoint region on chromosome 17 spans at least 80 kilobases.

Chromosome Walking

Localization of preferential sites of rearrangement within the BCR gene in Philadelphia chromosome-positive acute lymphoblastic leukemia.

The Philadelphia chromosome associated with acute lymphoblastic leukemia (ALL) has been linked to a hybrid BCR/ABL protein product that differs from that found in chronic myelogenous leukemia. This implies that the molecular structures of the two chromosomal translocations also differ. Localization of translocation breakpoints in Philadelphia chromosome-positive ALL has been impeded due to the only partial characterization of the BCR locus. We have isolated the entire 130-kilobase BCR genomic locus from a human cosmid library. A series of five single-copy genomic probes from the 70-kilobase first intron of BCR were used to localize rearrangements in 8 of 10 Philadelphia chromosome-positive ALLs. We have demonstrated that these breakpoints are all located at the 3' end of the intron around an unusual restriction fragment length polymorphism caused by deletion of a 1-kilobase fragment containing Alu family reiterated sequences. This clustering is unexpected in light of previous theories of rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia that would have predicted a random dispersion of breakpoints in the first intron in Philadelphia chromosome-positive ALL. The proximity of the translocation breakpoints to this constitutive deletion may indicate shared mechanisms of rearrangement or that such polymorphisms mark areas of the genome prone to recombination.

Base Sequence

Nonleukemic granulocytic sarcoma of the heart: a report of a fatal case.

We report the clinical and pathological features of a cardiac fatality caused by granulocytic sarcoma in a young adult man with no evidence of leukemia involving bone marrow or peripheral blood. At autopsy, walls of the four cardiac chambers were massively infiltrated by tumor, resulting in a cardiac weight of almost three times normal. Routine cytochemical stains plus immunoperoxidase staining for OKM1 confirmed the diagnosis. Although subclinical cardiac infiltrates are commonly detected at autopsy in patients with acute nonlymphoblastic leukemia (ANLL), massive cardiac granulocytic sarcoma in the absence of bone marrow disease has not been previously described. Cytochemical and immunological methods of diagnosing granulocytic sarcoma in fixed tissues are reviewed.

Adult

Endoscopic "salvage" cytology in neoplasms metastatic to the upper gastrointestional tract.

Endoscopic "salvage" cytology was the only successful nonoperative diagnostic method in two patients with malignancy metastatic to the upper gastrointestinal tract. Smears and cell blocks of centrifuged material aspirated from the endoscope channel provided diagnoses of malignancies when other diagnostic techniques had been nonproductive. The results in these cases support the general utility of this technique and indicate its successful application in this specific clinical setting.

Aged