Biomedical subjects

Janet D Rowley

Publications and source records attributed to Janet D Rowley.

40 records · Page 3Linked to original sources

PubMed2002

t(1;3)(p36;p21) is a recurring therapy-related translocation.

Chromosome bands 1p36 and 3p21 are known to be recurring breakpoints in therapy-related (t-) leukemia. We identified a recurring translocation, t(1;3)(p36;p21), in eight patients with various hematologic malignancies: three patients with ALL, one with chronic myelogenous leukemia (CML) in accelerated phase (AP), two with MDS, and two with AML(M3). Five of the eight patients had a history of chemotherapy, including alkylating agents in three, before the translocation was detected. In two of these five patients, the t(1;3)(p36;p21) emerged only at relapse or in the accelerated phase of CML. The karyotypes of the patients were complex, including -7 and structural abnormalities of 5q, 6q, 7q, 9p, and 11q23. Survival time varied among patients (25 days to more than 16 years). Using FISH with 13 1p35-36 cosmid probes (tel-FB12-CA5-G7-FD2-CB1-ED8-FD9-G32-AE3-G50-AD8-GG4-G43-cen), we delineated the 1p36 breakpoint in two patients with MDS and ALL as lying between FB12 and FD2 (between BAC47P3 and PAC963K15), with a small deletion near the breakpoint in both cases. In the patient with MDS, there was also a deletion at 3p21.3, as detected with the cosmid probe cosNRL9. The results of the present study suggest that t(1;3)(p36;p21) in hematologic diseases is associated with prior exposure to mutagens, including alkylating agents.

Adult↗

PubMed2002

A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndrome.

ETV6/TEL is the first transcription factor identified that is specifically required for hematopoiesis within the bone marrow. This gene has been found to have multiple fusion partners of which 16 have been cloned. Fluorescence in situ hybridization (FISH) analysis in a patient with myelodysplastic syndrome (MDS) revealed a t(1;12)(p36;p13) involving ETV6, with the breakpoint in this gene between exon 2 and exon 3. We report here the cloning of a novel ETV6 partner located on 1p36.1, involved in the t(1;12). 3' RACE-PCR from RNA identified a novel sequence fused to exon 2 of ETV6. Database searches localized this sequence in a bacterial artificial chromosome (BAC) mapped to 1p36 by fingerprint analysis. This result was confirmed by FISH using this BAC as probe. 5' and 3' RACE experiments with primers from this novel sequence were carried out on RNA from a healthy donor and identified a novel full-length mRNA, which we named MDS2 (myelodysplastic syndrome 2). RT-PCR experiments were performed on a panel of human cDNAs to analyze the expression pattern of this gene and they revealed four splicing variants. RT-PCR analysis showed that ETV6-MDS2, but not the reciprocal MDS2-ETV6 fusion transcript, was expressed in the bone marrow of the patient. The product of the ETV6-MDS2 fusion transcript predicts a short ETV6 protein containing the first 54 amino acids of ETV6 plus four novel amino acids, lacking both the PTN and the DNA-binding domains. Possible mechanisms to account for the development of MDS in this patient are discussed.

Aged↗

PubMed2002

Correct identification of genes from serial analysis of gene expression tag sequences.

SAGE (serial analysis of gene expression) is a remarkable technique for genome-wide analysis of gene expression. It is crucial to understand the extent to which SAGE can accurately indicate a gene or expressed sequence tag (EST) with a single tag. We analyzed the effect of the size of SAGE tag on gene identification. Our observation indicates that SAGE tags are in general not long enough to achieve the degree of uniqueness of identification originally envisaged. Our observations also indicate that the limitation of using SAGE tag to identify a gene can be overcome by converting SAGE tags into longer 3' EST sequences with the generation of longer cDNA fragments from SAGE tages for gene identification (GLGI) method.

Expressed Sequence Tags↗

PubMed2002

Therapy-related acute myeloid leukemia/myelodysplasia with balanced 21q22 translocations.

The morphologic and immunophenotypic findings of 36 cases of 21q22 acute myeloid leukemia (AML) and myelodysplasia (MDS) were compared, including 14 de novo t(8;21) AMLs, 11 t(8;21) therapy-related AML/MDS cases, and 11 therapy-related AML/MDS cases with other 21q22 balanced translocations [t(n;21)]. Cases were evaluated for the presence of Auer rods, distinct chunky cytoplasmic blast cell granules, promyelocyte increase, cytoplasmic perinuclear clearing (hofs) of blast cells, eosinophil increase, andfeatures of associated trilineage dysplasia. Results of immunophenotyping studies for CD19, CD34, and CD56 expression were compared. Cases of de novo and therapy-related t(8;21) disease shared common morphologic features of chunky cytoplasmic granules, perinuclear hofs, and promyelocyte increases that were not seen consistently in the t(n;21) group of t-AML/MDS cases. Immunophenotypic similarities also were observed between the 2 t(8;21) groups. De novo and therapy-related t(8;21) disease, however, differed by the frequent presence of associated dysplasia in both t-AML/MDS groups, which was infrequent in the de novo t(8;21) group. Therapy-related AMI/MDS with t(8;21) shares characteristic morphologic and immunophenotypic features with de novo t(8;21) AML, but frequently also occurs with associated myelodysplastic changes, similar to other therapy-related acute leukemias.

Antigens, CD19↗